Growth Hormone Improves Cognitive Function After Experimental Stroke

Ong, Lin Kooi; Chow, Wei Zhen; TeBay, Clifford; Kluge, Murielle G.; Pietrogrande, Giovanni; Zalewska, Katarzyna; Crock, Patricia; Åberg, N. David; Bivard, Andrew; Johnson, Sarah J.; Walker, Frederick R.; Nilsson, Michael; Isgaard, Jörgen

doi:10.1161/strokeaha.117.020557

Cited by 44 publications

(65 citation statements)

References 40 publications

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“…However, these positive effects of GH have been widely demonstrated in different experimental animal models [29,30,31,32,33]; even in old animals, in which the cognitive impairment of hippocampal-dependent functions, such as learning and memory, is associated with a decrease in the secretion of GH and IGF-I, as in our species [4,17,18,32]. …”

Section: Discussionmentioning

confidence: 99%

Treatment with Growth Hormone (GH) Increased the Metabolic Activity of the Brain in an Elder Patient, Not GH-Deficient, Who Suffered Mild Cognitive Alterations and Had an ApoE 4/3 Genotype

Devesa¹,

Núñez²,

Agra³

et al. 2018

IJMS

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(1) Background: We analyzed, using PET-SCAN and cognitive tests, how growth hormone (GH) could act in the brain of an older woman, not deficient in GH, who showed mild cognitive alterations (MCI) and had a genotype of ApoE 4/3 and familial dyslipidemia. (2) Methods: After performing a first psychometric study (TAVEC verbal learning test), the metabolic activity of brain structures related to knowledge, memory, and behavior was analyzed using 18-F fluorodeoxyglucose PET-SCAN. The patient was then treated with GH (0.4 mg/day, subcutaneous) for three weeks and on the last day under this treatment, a new PET-SCAN was performed. One month after beginning treatment with GH, a new TAVEC test was performed. (3) Results: GH administration normalized the cognitive deficits observed in the first psychometric test and significantly (p < 0.025) increased the metabolic activity in practically all brain cortical areas, specifically in the left hippocampus and left amygdala, although not in the left parahippocampus. (4) Conclusions: This study demonstrates for the first time the positive effects of GH on cerebral metabolism in a patient without GH deficiency, recovering the function of affected areas related to knowledge, memory, and behavior in an elderly patient with MCI.

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Section: Discussionmentioning

confidence: 99%

Treatment with Growth Hormone (GH) Increased the Metabolic Activity of the Brain in an Elder Patient, Not GH-Deficient, Who Suffered Mild Cognitive Alterations and Had an ApoE 4/3 Genotype

Devesa¹,

Núñez²,

Agra³

et al. 2018

IJMS

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“…IGF-I is also synthesized in the CNS [29], and its expression, induced by GH, has been detected in neural stem cells from fetal human forebrains [30]. Both GH and IGF-I play a very important reparative role after a brain injury, a hypothesis postulated a long time ago [31] and later proved by many preclinical and clinical studies, regardless of whether the experimental animals or human patients were GHD or not [32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49].…”

Section: Ghd and Nervous System Functioningmentioning

confidence: 99%

Growth Hormone Deficiency: Is It Just a Problem of Growth Impairment? Part I

Devesa¹

2020

Growth Disorders and Acromegaly

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The concept that the growth hormone (GH) is a merely metabolic pituitary hormone with effects on the longitudinal growth of the organism until the end of puberty has been questioned in recent years. We know today that the expression of GH also occurs in virtually all organs and tissues where it performs very important autocrine/paracrine and even intracrine functions. GH acts on all organs and tissues, being particularly important in the development of the brain during the fetal period. In addition, the hormone, after interacting with its membrane receptor, is internalized together with its receptor, allowing it to reach the cell nucleus where it acts as a transcription factor. In the first part of this review, we will analyze the effects of GH on the brain, the cardiovascular system, and the gonadal system, as well as the adverse effects that occur in the GH deficiency not treated in children and adults. GH is absolutely necessary for a normal brain development and also for repairing the nervous system after an injury. Moreover, GH plays a very important role in the cardiovascular system, as well as in normal gonadal functioning.

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“…Associative memory cognitive domain was assessed in mice using the touchscreen platform for PAL task. 18,19 Touchscreen operant chambers (Campden Instruments Ltd., UK, Figure 1(a)) were used in the testing, and by their nature are inherently blinded. 18,20 A liquid reward (strawberry milkshake; Paul's Milky Max) was provided to motivate animals' performance.…”

Section: Assessment Of Cognitive Deficitsmentioning

confidence: 99%

“…Matlab (R2015a, MathWorks) were used to quantitate tissue loss, cell count, Aquaporin-4 (APQ4) vessel/parenchymal ratio, and to analyse intensity and area coverage of immunolabelling. 16,17,19,[23][24][25] To estimate tissue loss within the infarcted hemisphere, the area of contralateral and ipsilateral hemispheres were measured across four sections (at Bregma level +1.0, 0.0, -1.0 and -2.0 mm, Figure 2 For the purposes of analysis, we calculated the percentage of cumulative threshold material for the range of pixel intensity values ( Figure 7). Pixel intensity level considered to be optimal for detecting genuine differences in immunoreactive signal was determined using ImageJ software to visualize thresholding of cropped regions at individual pixel intensities.…”

Section: Image Acquisition Tissue Loss Cell Count Thresholding Andmentioning

confidence: 99%

“…The vessel digital reconstruction was performed as previously described. 19,26,27 Collagen IV positive cells were isolated from the background using multi-level Otsu's thresholding method, which calculates the threshold that minimizes the interclass pixel intensity variance between groups. Using Matlab functions we determined percentage area covered by the labelling.…”

Section: Image Acquisition Tissue Loss Cell Count Thresholding Andmentioning

confidence: 99%

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Low oxygen post conditioning improves stroke-induced cognitive impairment

Zhao

Ong

Pietrogrande

et al. 2018

Preprint

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Post-stroke cognitive impairment has proven to be notoriously difficult to treat. In the current study, we sought to both better understand cellular changes that underpin cognitive deficits and to consider the potential restorative benefits of low oxygen post conditioning (LOPC).We were motivated to use LOPC as an intervention as it is one of the few experimental interventions previously shown to improve cognitive function post-stroke. Experimental stroke was induced by photothrombotic occlusion in adult male C57BL/6 mice. Mice were randomly assigned to either a normal atmospheric air exposure or low oxygen (11% O 2 ) exposure groups three days post-occlusion. On day 17 post-stroke, mice were euthanized for histology or biochemical analyses. Stroked mice exposed to LOPC was associated with marked reductions in amyloid-beta both in its absolute level and in the extent of its oligomerization. Exposure to LOPC post-stroke also improved cellular deficits induced by stroke including an increase in vessel density, a reduction in vascular leakage, and restoration of AQP4 polarisation. Critically, stroked mice exposed to LOPC exhibited robust improvements in cognitive function post-stroke, assessed using a touchscreen based pairedassociate learning task. These findings provide compelling pre-clinical evidence of the potential clinical utility of LOPC for enhancing recovery post-stroke.

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Growth Hormone Improves Cognitive Function After Experimental Stroke

Abstract: These findings provide compelling preclinical evidence for the usage of GH as a potential therapeutic tool in the recovery phase of patients after stroke.

Cited by 44 publications

References 40 publications

Treatment with Growth Hormone (GH) Increased the Metabolic Activity of the Brain in an Elder Patient, Not GH-Deficient, Who Suffered Mild Cognitive Alterations and Had an ApoE 4/3 Genotype

Treatment with Growth Hormone (GH) Increased the Metabolic Activity of the Brain in an Elder Patient, Not GH-Deficient, Who Suffered Mild Cognitive Alterations and Had an ApoE 4/3 Genotype

Growth Hormone Deficiency: Is It Just a Problem of Growth Impairment? Part I

Low oxygen post conditioning improves stroke-induced cognitive impairment

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