Motor Improvement of Skilled Forelimb Use Induced by Treatment with Growth Hormone and Rehabilitation Is Dependent on the Onset of the Treatment after Cortical Ablation

Abstract

We previously demonstrated that the administration of GH immediately after severe motor cortex injury, in rats, followed by rehabilitation, improved the functionality of the affected limb and reexpressed nestin in the contralateral motor cortex. Here, we analyze whether these GH effects depend on a time window after the injury and on the reexpression of nestin and actin. Injured animals were treated with GH (0.15 mg/kg/day) or vehicle, at days 7, 14, and 35 after cortical ablation. Rehabilitation was applied at short and long term (LTR) after the lesion and then sacrificed. Nestin and actin were analyzed by immunoblotting in the contralateral motor cortex. Giving GH at days 7 or 35 after the lesion, but not 14 days after it, led to a remarkable improvement in the functionality of the affected paw. Contralateral nestin and actin reexpression was clearly higher in GH-treated animals, probably because compensatory brain plasticity was established. GH and immediate rehabilitation are key for repairing brain injuries, with the exception of a critical time period: GH treatment starting 14 days after the lesion. Our data also indicate that there is not a clear plateau in the recovery from a brain injury in agreement with our data in human patients.

Growth Hormone (GH) and Gonadotropin-Releasing Hormone (GnRH) in the Central Nervous System: A Potential Neurological Combinatory Therapy?

“…There were clear implications of GH in the opioid system function in which it was able to decrease levels of the delta-opioid receptor in layers I–IV of the cerebral cortex [ 87 ]. In brain trauma, GH has demonstrated neurotrophic actions in the cognitive, sensorial, and motor functions [ 57 , 58 , 88 , 89 ]. In an experimental model for brain contusion recovery, GH improved cognitive function and increased the brain-derived neurotrophic factor (BDNF) and TrkB in the prefrontal area [ 73 ].…”

Cognitive Evolution of a Patient Who Suffered a Subarachnoid Haemorrhage Eight Years Ago, after Being Treated with Growth Hormone, Melatonin and Neurorehabilitation

“…During the post-acute period these hormones also improve the lost cognitive functions; specific neurostimulation, including EINA, is of great help for enhancing the neuroregenerative effects of GH and facilitating the creation of new neuronal circuits that would replace the lost ones after the SAH, perhaps because facilitating brain plasticity, as we recently demonstrated in rats treated with GH after a severe frontal motor cortex ablation [36,64].…”

Growth Hormone Promotes Motor Function after Experimental Stroke and Enhances Recovery-Promoting Mechanisms within the Peri-Infarct Area

“…Furthermore, there is now building evidence demonstrating that GH treatment in addition to standard rehabilitation can significantly contribute to the motor recovery of an acquired brain injury [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24]37,46,47]. For instance, Heredia et al [18,37] observed that administration of GH subcutaneously together with rehabilitation significantly improved motor function in rats as measured by the paw-reaching-for-food task. Therefore, we were motivated to extend the existing preclinical literature to consider GH treatment for its ability to ameliorate motor impairments after stroke [14].…”

“…The therapeutic potential of GH on brain repair after brain injury or stroke has been considered in both human [9][10][11][12][13][14][15][16][17][18] and preclinical [19][20][21][22][23][24] studies. GH, a peptide hormone released from the anterior pituitary gland, plays an important role in brain growth, development and function [11].…”

“…However, this self-repair mechanism operates only acutely after stroke and is insufficient to promote long-term recovery. Interestingly, several experimental studies have shown that GH can promote these neurorestorative or plasticity-promoting processes beyond what occurs with spontaneous recovery after brain injury or stroke, and this increased neurorestoration is closely linked with improvement in functional outcomes [9,11,15,18,37,38]. Despite the fact that the positive effects of GH in the adult brain have been extensively studied, it is still not clear whether GH could promote motor function after stroke.…”