Efficacy of Thyrotropin-Releasing Hormone Analog for Protracted Disturbance of Consciousness due to Aneurysmal Subarachnoid Hemorrhage

Shibata, Ami; Matano, Fumihiro; Fujiki, Yu; Mizunari, Takayuki; Murai, Yasuo; Morita, Akio

doi:10.1016/j.jstrokecerebrovasdis.2018.12.036

Cited by 2 publications

(4 citation statements)

References 21 publications

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“…TRH mimetics have been shown to be useful in the treatment of spinocerebellar degeneration ( Shimizu et al, 2020 ; Ijiro et al, 2022 ), amyotrophic lateral sclerosis ( Hawley et al, 1987 ), spinal muscular atrophy ( Kat o et al, 2009 ), prolonged disturbance of consciousness due to aneurysmal subarachnoid hemorrhage ( Shibata et al, 2019 ), Parkinson’s disease ( Zheng et al, 2018a ; Zheng et al, 2018b ), epilepsy ( Rajput et al, 2009 ; Sah et al, 2011 ), psychiatric disorders with underlying inflammatory processes ( Kamath, 2012 ), and possibly depression ( Duval et al, 2021 ). The effects of TRH and its analogs on the CNS are usually achieved in cooperation with the modulatory effects of neurotransmitters such as glutamate, dopamine, norepinephrine, acetylcholine, serotonin, or GABA.…”

Section: Thyrotropin-releasing Hormone Receptor Ligands and Their Pha...mentioning

confidence: 99%

Biochemical and physiological insights into TRH receptor-mediated signaling

Trubacova

Drastichova

Novotný

2022

Front. Cell Dev. Biol.

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Thyrotropin-releasing hormone (TRH) is an important endocrine agent that regulates the function of cells in the anterior pituitary and the central and peripheral nervous systems. By controlling the synthesis and release of thyroid hormones, TRH affects many physiological functions, including energy homeostasis. This hormone exerts its effects through G protein-coupled TRH receptors, which signal primarily through Gq/11 but may also utilize other G protein classes under certain conditions. Because of the potential therapeutic benefit, considerable attention has been devoted to the synthesis of new TRH analogs that may have some advantageous properties compared with TRH. In this context, it may be interesting to consider the phenomenon of biased agonism and signaling at the TRH receptor. This possibility is supported by some recent findings. Although knowledge about the mechanisms of TRH receptor-mediated signaling has increased steadily over the past decades, there are still many unanswered questions, particularly about the molecular details of post-receptor signaling. In this review, we summarize what has been learned to date about TRH receptor-mediated signaling, including some previously undiscussed information, and point to future directions in TRH research that may offer new insights into the molecular mechanisms of TRH receptor-triggered actions and possible ways to modulate TRH receptor-mediated signaling.

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Section: Thyrotropin-releasing Hormone Receptor Ligands and Their Pha...mentioning

confidence: 99%

Biochemical and physiological insights into TRH receptor-mediated signaling

Trubacova

Drastichova

Novotný

2022

Front. Cell Dev. Biol.

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“…In evaluating TRH’s analeptic actions, concussed mice (by the impact of bakelite rod) that received intramuscular or intravenous injections of TRH tartrate (TRH-T) (0.04–5 mg/kg) in the tail vein showed a decrease in latency for displaying spontaneous movement and right reflexes [ 27 , 42 ]. Additionally, 40% of patients with disturbed consciousness improve their symptoms after 10 days of intramuscular or intravenous administration of TRH-T (0.5–2 mg/kg).…”

Section: Introductionmentioning

confidence: 99%

“…Given that previous attempts to evaluate the effectiveness of a TRH-T therapy for protracted disturbances of consciousness are not consistent, recent studies have analyzed the effects of intravenous injections of TRH-T (2 mg/kg) over 2 days in patients with cerebral aneurysm-induced subarachnoid hemorrhage, which may develop neurological alterations [ 27 ]. For evaluating the consciousness disturbance and cognitive function of 32 patients, researchers use the score obtained with the Hasegawa dementia rating scale (revised) (HDS-R).…”

Section: Introductionmentioning

confidence: 99%

“…Some 61% of the TRH-T-treated group presented a greater increase in the HDS-R score, which is classified as a good outcome. Some demographic characteristics of patients, such as age (≥60 years) and an initial HDS-R score below 4, represent a risk of obtaining poor responses to TRH-T treatment [ 27 ]. These are important aspects to be considered when evaluating the efficacy of TRH-T therapy, because when they are not taken into account, inconsistent outcomes may result.…”

Section: Introductionmentioning

confidence: 99%

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New Efforts to Demonstrate the Successful Use of TRH as a Therapeutic Agent

Alvarez-Salas

García-Luna

Gortari

2023

IJMS

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Thyrotropin-releasing hormone (TRH) is a tripeptide that regulates the neuroendocrine thyroid axis. Moreover, its widespread brain distribution has indicated that it is a relevant neuromodulator of behaviors such as feeding, arousal, anxiety, and locomotion. Importantly, it is also a neurotrophic peptide, and thus may halt the development of neurodegenerative diseases and improve mood-related disorders. Its neuroprotective actions on those pathologies and behaviors have been limited due to its poor intestinal and blood–brain barrier permeability, and because it is rapidly degraded by a serum enzyme. As new strategies such as TRH intranasal delivery emerge, a renewed interest in the peptide has arisen. TRH analogs have proven to be safe in animals and humans, while not inducing alterations in thyroid hormones’ levels. In this review, we integrate research from different approaches, aiming to demonstrate the therapeutic effects of TRH, and to summarize new efforts to prolong and facilitate the peptide’s actions to improve symptoms and the progression of several pathologies.

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Efficacy of Thyrotropin-Releasing Hormone Analog for Protracted Disturbance of Consciousness due to Aneurysmal Subarachnoid Hemorrhage

Cited by 2 publications

References 21 publications

Biochemical and physiological insights into TRH receptor-mediated signaling

Biochemical and physiological insights into TRH receptor-mediated signaling

New Efforts to Demonstrate the Successful Use of TRH as a Therapeutic Agent

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