Effects of RGH-2202 on behavioral deficits after focal cerebral ischemia in rats

Noda, Yukihiro; Furukawa, Kiyoshi; Kohayakawa, Hitoshi; Oka, Makoto

doi:10.1016/0091-3057(95)00134-i

Cited by 17 publications

(2 citation statements)

References 16 publications

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“…These findings are supported by another observation of delayed functional recovery after cessation of TRH administration 224 . This delayed effect on functional recovery could be related to the activation of NSPCs, leading to neuronal regeneration and/or modulation of the post-ischemic environment.…”

Section: Trh Stimulates Proliferation In Nspcssupporting

confidence: 79%

Efficient non-viral transfection of adult neural stem/progenitor cells, without affecting viability, proliferation or differentiation

2005

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Stroke is one of the leading causes of chronic disability and death in the Western world. Today, no treatment can repair the cellular loss associated with an ischemic lesion. However, the discovery and dynamic regulation of neural stem/progenitor cells in the adult mammalian brain has resulted in exciting possibilities for future therapeutic interventions. Endogenous or grafted neural stem/progenitor cells are activated following an ischemic insult. These cells undergo directed migration towards infarcted areas, and differentiate in response to the insult. Unfortunately, the results of this regenerative effort are limited compared to the amount of tissue loss. This could be due to low survival of the recruited cells, but could also be explained by insufficient activation or dysfunctional lineage selection. Whether the lineage selection of neural stem/progenitor cells is altered following a lesion in the brain, what signals that are responsible for their activation or whether these cells can participate in post-lesion regeneration, astrogliosis or neuroprotection have yet to become clear. A greater understanding of these processes is necessary for finding ways to improve the endogenous regenerative capacity. We found that reactive astrocytes, a prominent part of the post-ischemic environment, induced astroglial differentiation of adult neural stem/progenitor cells in vitro. Moreover, astrocytes derived from these cells were shown to participate in glial scar formation in vitro. After studying gene expression in the peri-infarct region following focal ischemia, the expression of several genes was induced. We chose to focus our attention on one of these genes and its product, thyrotropin-releasing hormone (TRH). Immunoreactivity for TRH was found in several areas in both lesioned and intact brain regions, including in microglia present in the areas surrounding the lesion. Furthermore, TRH receptors were expressed on cultured neural stem/progenitor cells and TRH potently induced the proliferation of these cells. TRH is an interesting target for stroke treatment, but it also has many central effects in the brain and systemic administration may prove problematic. An interesting protocol for local delivery of TRH would be by grafting stem/progenitor cells, genetically engineered to secrete the peptide. In order to create a foundation for neuroprotective gene therapy, we developed efficient methods for non-viral transfection of neural stem/progenitor cells. Since neural stem/progenitor cells migrate towards the ischemic area we wanted to investigate whether these cells secreted factors that could protect neurons against excitotoxicity, the main inducer of cell death following a stroke. Mass spectrometric analysis of factors secreted from cultured neural stem/progenitor cells led to the identification of a novel neuroprotective peptide, which we termed pentinin. This peptide potently reduced excitotoxicity in both mature and immature neurons in an ex vivo hippocampal slice model. The results presented in this the...

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Section: Trh Stimulates Proliferation In Nspcssupporting

confidence: 79%

Efficient non-viral transfection of adult neural stem/progenitor cells, without affecting viability, proliferation or differentiation

2005

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“…During the years of development of the various kinds of TRH analogues, it was found that in order to maintain the neuroprotective effects of TRH, it is crucial to conserve the L-ProNH 2 residue [17,19]. The neuroprotective effects of TRH and its analogues (tartelin, montirelin, RGH-2202), were demonstrated in animals models of traumatic brain and spinal cord injury, as well in ischemia [2,5,16,36,39,40,51]. Studies with cyclic derivates of the TRH metabolite CHP, showed their efficiency as an antiexcitotoxic, anti-necrotic and anti-apoptotic agent in neuronal cells [16][17][18]49].…”

Section: Trh Analogues and Neuroprotectionmentioning

confidence: 99%

Tyreoliberin (Trh) – The Regulatory Neuropeptide of Cns Homeostasis

Jantas¹

2010

Advances in Cell Biology

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Summary:The physiological role of thyreoliberin (TRH) is the preservation of homeostasis within four systems (i) the hypothalamic-hypophsysiotropic neuroendocrine system, (ii) the brain stem/midbrain/spinal cord system, (iii) the limbic/cortical system, and (iv) the chronobiological system. Thus TRH, via various cellular mechanisms, regulates a wide range of biological processes (arousal, sleep, learning, locomotive activity, mood) and possesses the potential for unique and widespread applications for treatment of human illnesses. Since the therapeutic potential of TRH is limited by its pharmacological profile (enzymatic instability, short half-life, undesirable effects), several synthetic analogues of TRH were constructed and studied in mono-or adjunct therapy of central nervous system (CNS) disturbances. The present article summarizes the current state of understanding of the physiological role of TRH and describes its putative role in clinical indications in CNS maladies with a focus on the action of TRH analogues.

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Posatirelin (l-pyro-2-aminoadipyl-l-leucyl-l-prolinamide) treatment for persons with dementia

Culum

Forbes

2008

Cochrane Database of Systematic Reviews

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Effects of RGH-2202 on behavioral deficits after focal cerebral ischemia in rats

Cited by 17 publications

References 16 publications

Efficient non-viral transfection of adult neural stem/progenitor cells, without affecting viability, proliferation or differentiation

Efficient non-viral transfection of adult neural stem/progenitor cells, without affecting viability, proliferation or differentiation

Tyreoliberin (Trh) – The Regulatory Neuropeptide of Cns Homeostasis

Posatirelin (l-pyro-2-aminoadipyl-l-leucyl-l-prolinamide) treatment for persons with dementia

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