Growth Hormone Treatment Promotes Remote Hippocampal Plasticity after Experimental Cortical Stroke

Abstract

Cognitive impairment is common after stroke, and disturbances in hippocampal function are often involved, even in remote non-hippocampal injuries. In terms of hippocampal function, growth hormone (GH) is known to affects plasticity and cognition. We aimed to investigate whether GH treatment after an experimental cortical stroke could enhance remote hippocampal plasticity and the hippocampal-dependent visual discrimination task. C57BL6 male mice were subjected to cortical photothrombotic stroke. Stroke mice were then treated with either saline or GH at 48 h after occlusion for 28 days. We assessed learning and memory using mouse touchscreen platform for the visual discrimination task. We also evaluated markers of neural progenitor cells, synaptic plasticity and cerebrovascular remodelling in the hippocampal formation. GH treatment significantly improved the performance on visual discrimination task after stroke. We observed a concomitant increased number of bromodeoxyuridine-positive cells in the dentate gyrus of the hippocampus. We also detected increased protein levels and density of doublecortin, a neuronal precursor cells marker, as well as glutamate receptor 1 (GLuR1), a synaptic marker. These findings provide further neurobiological evidence for how GH treatment could be used to promote hippocampal plasticity in a remote region from the initial cortical injury, and thus enhance cognitive recovery after stroke.

Exploring How Low Oxygen Post Conditioning Improves Stroke-Induced Cognitive Impairment: A Consideration of Amyloid-Beta Loading and Other Mechanisms

“…Although promising, the use of individual pharmacological strategies e.g., donepezil and memantine, have a patchy record of success ( 2 ). Recent evidence has shown pro-cognitive effects of exogenously delivered growth hormone post-stroke ( 6 – 9 ). Another equally promising pro-cognitive therapy has been the use of intermittent exposure to a reduced oxygen environment ( 10 , 11 ).…”

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

“…Therefore, endogenous GH/IGF-I axis or exogenously administered GH or IGF-I act in neuroprotection, neurogenesis, angiogenesis, and synaptogenesis [ 22 , 34 , 35 , 36 , 37 , 38 , 39 ], as well as modulate neurotransmission through the synuclein (SYN) signal [ 36 ] and increases key mechanisms for a series of brain functions [ 28 , 37 , 38 , 39 ] and brain repair after an injury [ 34 , 36 , 37 ]. These reasons led to the use of GH or IGF-I in different models of brain injuries [ 34 , 35 , 36 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 ]. Regardless of the fact that TBI can produce GH-deficiency (GHD) [ 42 ], which contributes to the cognitive sequelae associated with TBI [ 43 ], and GH treatment in rats after TBI improves their cognitive, motor and behavioral activities [ 45 , 46 , 47 ].…”

“…All of these effects reduce the symptoms caused by TBI and provide cognitive improvements [ 9 , 46 , 47 ], motor improvements, beneficial behavioral and psychological effects (reduces anxiety, depression, sleep disorders) and improves quality of life [ 48 , 49 ]. These positive results can be seen in both the short and long term and are like those seen with GH treatment in ischemia and stroke [ 50 , 51 ].…”

Similar cognitive deficits in mice and humans in the chronic phase post-stroke identified using the touchscreen-based paired-associate learning task

“…Our group has previously reported on the use of the rodent touchscreen platform to assess cognitive decline in mice after photothrombotic stroke 18 – 20 . We demonstrated that the rodent touchscreen platform constitutes a pertinent assessment tool which is sensitive to the effects of pharmacological/therapeutic interventions to improve cognitive function after stroke 19 – 21 . The major question that we wanted to address was “do mice and humans in the chronic phase post-stroke respond similarly when evaluated using touchscreen delivered PAL task?” The aim of the present study was to apply and in parallel evaluate the touchscreen-based visuospatial object-location PAL task in chronic stroke survivors and in mice in chronic phase after experimental stroke.…”