Rats with brain injuries respond to growth hormone therapy

José Pichel Andrés/DICYT A study has proved the effectiveness of growth hormone therapy combined with rehabilitation in adult rats with brain injuries. The animals recover their motor functions when treatment is given immediately after the brain injury is produced, according to an article by researchers of the Universidad de Salamanca (Spain) published in Behavioural Brain Researh.

Margarita Hereida, scientist at the Department of Physiology and Pharmacology of the Universidad de Salamanca, member of the Instituto de Neurociencias de Castilla y León (INCyL) and first author of the article, explained to DiCYT that this study continues the research by her team during the last few years on the benefits of neural transplants in rat models with injuries at the motor cortex, a part of the brain cortex controlling and performing voluntary movements.

In this model, animals are taught fine motor skill behaviors: to take a leg out through one of the holes in the test box to get to the food placed outside in a feeding trough.

Once this behavior is learnt, a suction injury is performed at the contralateral motor cortex to the better leg, that is, in right-handed rats they produce injuries in the left hemisphere and, in left-handed rats injuries are produced in the right hemisphere, since each cerebral hemisphere controls the opposite limb. After determining the injury is effective, they proceed to neural transplants.

The researchers started to perform these transplants using embryonic tissue from the same brain area, proving there was a recovery of motor functions; they also studied the mechanisms involved in the recovery by using different types of non-cortical donor tissues, such as tonsil tissue and striatum tissue.

In order to perform these studies on humans, considering ethical and legal issues associated with the use of embryonic tissues, these scientists considered some other strategies. One of the strategies was using astrocytes, a type of glial cell encapsulated in alginate beads, a biocompatible polymer.

Nevertheless, the quest for new strategies was altered by Jesús Devesa, researcher at the Universidade de Santiago de Compostela and pioneer in growth hormone clinical therapies. “We came in contact with him to use his method in our experimental model,” Margarita Heredia states.

All in all, this new research stage lies in supplying growth hormone combined with rehabilitation to adult rats conditioned to perform a fine motor skill test and whose motor cortex has been injured by suction (injures proven effective).

In order to perform these experiments, rats were divided into several groups. One of them was given growth hormone immediately after injuries were produced; other was given the hormone after six days. Results were corroborated by control groups; the first group recovered from motor conditions and the second group did not.

The rehabilitation process consists in forcing the use of the leg affected by injuries; it was performed in two periods: between 5 and 14 days after injuries and 30 days after growth hormone therapy. Researchers are considering other timeframes.

Molecular Mechanisms

Furthermore, the research has also included immunohistochemical studies to locate substances involved in these processes. One of the substances is glial fibrillary acidic protein (GFAP), rising after injuries due to the astrocytic reaction in the injured area.

The study has also focused on nestin, a protein expressed in puberty age in neural progenitor cells and, in adulthood is mainly found in the brain at places where stem cells are located, such as the lateral ventricles and the hippocampus. The experiment has proved nestin is re-expressed after injuries. “We found it in the undamaged hemisphere motor cortex; a fact we interpreted as evidence of plasticity”, as Adelaida Sánchez Riolobos, another researcher in the team, stated. This means that “nestin’s re-expression in the undamaged hemisphere contralateral cortex could be contributing to recovery”.

After this publication, researchers at the Universidad de Salamanca are considering new experiments to start rehabilitation from the first day of growth hormone therapy and to analyze the role of growth hormone receptors.

	References
	Heredia M, Fuente A, Criado J, Yajeya J, Devesa J, Riolobos AS. Early growth hormone (GH) treatment promotes relevant motor functional improvement after severe frontal cortex lesion in adult rats. Behavioural Brain Research, 2013. DOI: doi: 10.1016/j.bbr.2013.03.012