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

Abstract

Motor impairment is the most common and widely recognised clinical outcome after stroke. Current clinical practice in stroke rehabilitation focuses mainly on physical therapy, with no pharmacological intervention approved to facilitate functional recovery. Several studies have documented positive effects of growth hormone (GH) on cognitive function after stroke, but surprisingly, the effects on motor function remain unclear. In this study, photothrombotic occlusion targeting the motor and sensory cortex was induced in adult male mice. Two days post-stroke, mice were administered with recombinant human GH or saline, continuing for 28 days, followed by evaluation of motor function. Three days after initiation of the treatment, bromodeoxyuridine was administered for subsequent assessment of cell proliferation. Known neurorestorative processes within the peri-infarct area were evaluated by histological and biochemical analyses at 30 days post-stroke. This study demonstrated that GH treatment improves motor function after stroke by 50%–60%, as assessed using the cylinder and grid walk tests. Furthermore, the observed functional improvements occurred in parallel with a reduction in brain tissue loss, as well as increased cell proliferation, neurogenesis, increased synaptic plasticity and angiogenesis within the peri-infarct area. These findings provide new evidence about the potential therapeutic effects of GH in stroke recovery.

Growth Hormone Treatment Promotes Remote Hippocampal Plasticity after Experimental Cortical Stroke

“…However, we only investigated the neurorestorative effects of GH treatment within the peri-infarct regions [ 24 ]. The observed enhancement of recovery-promoting mechanisms within the peri-infarct area is most likely contributing to the improvement in motor outcomes [ 25 ], whereas the promotion of hippocampal neurogenesis and increased synaptic plasticity reported here are likely to be of importance for improved cognition.…”

“…Thirdly, we explored the effect of GH treatment on cerebrovascular remodeling. In our previous studies, we showed that GH has the ability to enhance angiogenesis, and increases the density and area coverage of both CD31 and Collagen IV–positive cells in the peri-infarct region [ 24 , 25 ]. In the current study, we analyzed vessel density in the hippocampus area using immunofluorescence labelled tomato lectin.…”

“…Sample size was estimated using G*Power 3.1 software. Using previous and preliminary data [ 24 , 25 ], we obtained an effect size of d = 1.6. Allowing a type 1 error of 5%, α = 0.05, with the power of 80%, β = 0.2, we calculated a samples size of 8 animals per group.…”

“…Mini-osmotic pump (Model 2004, Alzet, Cupertino, CA, USA) placement was performed as preciously described [ 24 , 25 , 59 ]. At D2, the mini-osmotic pumps were implanted.…”

“…Importantly, we have recently shown that GH treatment after photothrombotic vascular occlusion of the somatosensory and motor cortex promoted a marked improvement in the performance of associative memory cognitive domain as measured by the paired-associate learning task [ 24 ]. We additionally found an enhancement of neurorestorative processes, such as increased cell proliferation, neurogenesis, increased synaptic plasticity, myelination and angiogenesis within the peri-infarct region, most likely contributing to the improvement in motor outcomes [ 24 , 25 , 26 , 27 , 28 ]. However, we did not investigate the pro-cognitive effects of GH treatment on other cognitive domains and possible neurorestorative changes in the hippocampus.…”