Targeting different pathophysiological events after traumatic brain injury in mice: Role of melatonin and memantine

Keleştemur, Taha; Yuluğ, Burak; Caglayan, Ahmet Burak; Beker, Mustafa Çağlar; Kılıç, Ülkan; Yalçın, Esra; Gundogdu, Reyhan Zeynep; Kılıç, Ertuğrul

doi:10.1016/j.neulet.2015.11.043

Cited by 22 publications

(12 citation statements)

References 43 publications

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“…The global interest in evaluating the therapeutic effects of MEL after TBI is evident by the worldwide research conducted on this topic, including 8 studies from Turkey [ 20 , 24 , 29 , 30 , 31 , 32 , 33 , 34 ], 4 from the United States [ 35 , 36 , 37 ], 3 from China [ 38 , 39 ], 2 from Iran [ 40 , 41 ], 2 from Israel [ 42 , 43 ], 1 from France [ 44 ], 1 from Germany [ 44 ], and 1 from Italy [ 45 ].…”

Section: Resultsmentioning

confidence: 99%

“…The majority of the studies used rats, most commonly Sprague-Dawley rats [ 29 , 30 , 31 , 35 , 36 , 39 , 46 , 47 , 48 ] or Wistar rats [ 20 , 24 , 32 , 33 ]; N -Mary rats were used in 1 study [ 41 ] and NMRI rats used in another [ 40 ]. Less commonly, mice were used as the test animals, including the following strains: CD1 mice [ 39 , 45 ], Sabra mice [ 42 ], BALB/c [ 34 ], C57BL/6 mice [ 49 , 50 ], and Swiss mice [ 44 ]. Most of the studies conducted experiments on adult test animals with two exceptions testing the effects of childhood TBI [ 20 , 24 ]; one study did not specify the age of the test animals [ 33 ].…”

Section: Resultsmentioning

confidence: 99%

“…The second most common method of inducing TBI in the MEL literature was controlled cortical impact (CCI), which was used in 6 studies [ 36 , 39 , 44 , 45 , 50 , 51 ]. Less commonly used models include surgical brain injury [ 35 ], fluid percussion injury [ 46 ], and cold-probe injury [ 34 ].…”

Section: Resultsmentioning

confidence: 99%

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Melatonin as a Therapy for Traumatic Brain Injury: A Review of Published Evidence

Osier

McGreevy

Pham

et al. 2018

IJMS

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Melatonin (MEL) is a hormone that is produced in the brain and is known to bind to MEL-specific receptors on neuronal membranes in several brain regions. MEL’s documented neuroprotective properties, low toxicity, and ability to cross the blood-brain-barrier have led to its evaluation for patients with traumatic brain injury (TBI), a condition for which there are currently no Food and Drug Administration (FDA)-approved therapies. The purpose of this manuscript is to summarize the evidence surrounding the use of melatonin after TBI, as well as identify existing gaps and future directions. To address this aim, a search of the literature was conducted using Pubmed, Google Scholar, and the Cochrane Database. In total, 239 unique articles were screened, and the 22 preclinical studies that met the a priori inclusion/exclusion criteria were summarized, including the study aims, sample (size, groups, species, strain, sex, age/weight), TBI model, therapeutic details (preparation, dose, route, duration), key findings, and conclusions. The evidence from these 22 studies was analyzed to draw comparisons across studies, identify remaining gaps, and suggest future directions. Taken together, the published evidence suggests that MEL has neuroprotective properties via a number of mechanisms with few toxic effects reported. Notably, available evidence is largely based on data from adult male rats and, to a lesser extent, mice. Few studies collected data beyond a few days of the initial injury, necessitating additional longer-term studies. Other future directions include diversification of samples to include female animals, pediatric and geriatric animals, and transgenic strains.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Melatonin as a Therapy for Traumatic Brain Injury: A Review of Published Evidence

Osier

McGreevy

Pham

et al. 2018

IJMS

View full text Add to dashboard Cite

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“…Existing evidence shows endogenous MEL levels are altered in TBI-survivors in a time-point and biosample-dependent manner [11,12]; thus, MEL may be important in the body’s response to TBI and there may be an opportunity to improve outcomes via therapeutic administration of MEL. Pre-clinical studies have found MEL leads to attenuation of one or more of the histopathological and functional consequences of TBI [13,14]. Moreover, published evidence suggests that MEL has many mechanisms of action, including anti-apoptotic [15,16], anti-oxidative [17], and anti-mitophagic [18] properties; notably, the abovementioned pathways are all well-established as implicated in TBI-pathology.…”

Section: Introductionmentioning

confidence: 99%

Brain injury results in lower levels of melatonin receptors subtypes MT1 and MT2

Osier

Pham

Pugh

et al. 2017

Neuroscience Letters

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Background Traumatic brain injury (TBI) is a devastating and costly acquired condition that affects individuals of all ages, races, and geographies via a number of mechanisms. The effects of TBI on melatonin receptors remains unknown. Purpose The purpose of this study is to explore whether endogenous changes in two melatonin receptor subtypes (MT1 and MT2) occur after experimental TBI. Sample A total of 25 adult male Sprague Dawley rats were used with 6 or 7 rats per group. Methods Rats were randomly assigned to receive either TBI modeled using controlled cortical impact or sham surgery and to be sacrificed at either 6- or 24- hours post-operatively. Brains were harvested, dissected, and flash frozen until whole cell lysates were prepared, and the supernatant fluid aliquoted and used for western blotting. Primary antibodies were used to probe for melatonin receptors (MT1 and MT2), and beta actin for a loading control. ImageJ and Image Lab software were used to quantify the data which was analyzed using t-tests to compare means. Results Melatonin receptors levels were reduced in a brain region- and time point-dependent manner. Both MT1 and MT2 were reduced in the frontal cortex at 24 hours and in the hippocampus at both 6 hours and 24 hours. Discussion MT1 and MT2 are less abundant after injury, which may alter response to MEL therapy. Studies characterizing MT1 and MT2 after TBI are needed, including exploration of the time course and regional patterns, replication in diverse samples, and use of additional variables, especially sleep-related outcomes. Conclusion TBI in rats resulted in lower levels of MT1 and MT2; replication of these findings is necessary as is evaluation of the consequences of lower receptor levels.

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“…The neuroprotective role of minocycline has been confirmed in various animal models. In agreement with this, there are increasing data suggesting that minocycline exerts strong neuroprotective effects in translational experimental models which are relevant to human brain and spinal trauma [ 8 - 10 ]. For instance, a recent study indicated that minocycline blocked the neuronal cell death which was induced by optic nerve axotomy.…”

Section: Discussionmentioning

confidence: 64%

Minocycline Increases in-vitro Cortical Neuronal Cell Survival after Laser Induced Axotomy

Yuluğ

Ozansoy

Alokten

et al. 2020

CCP

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Background: Antibiotic therapies targeting multiple regenerative mechanisms have the potential for neuroprotective effects, but the diversity of experimental strategies and analyses of non-standardised therapeutic trials are challenging. In this respect, there are no cases of successful clinical application of such candidate molecules when it comes to human patients. Methods: After 24 hours of culturing, three different minocycline (Sigma-Aldrich, M9511, Germany) concentrations (1 μM, 10 μM and 100 μM) were added to the primary cortical neurons 15 minutes before laser axotomy procedure in order to observe protective effect of minocycline in these dosages. Results: Here, we have shown that minocycline exerted a significant neuroprotective effect at 1 and 100μM doses. Beyond confirming the neuroprotective effect of minocycline in a more standardised and advanced in-vitro trauma model, our findings could have important implications for future studies that concentrate on the translational block between animal and human studies. Conclusion: Such sophisticated approaches might also help to conquer the influence of humanmade variabilities in critical experimental injury models. To the best of our knowledge, this is the first study showing that minocycline increases in-vitro neuronal cell survival after laser-axotomy.

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Targeting different pathophysiological events after traumatic brain injury in mice: Role of melatonin and memantine

Cited by 22 publications

References 43 publications

Melatonin as a Therapy for Traumatic Brain Injury: A Review of Published Evidence

Melatonin as a Therapy for Traumatic Brain Injury: A Review of Published Evidence

Brain injury results in lower levels of melatonin receptors subtypes MT1 and MT2

Minocycline Increases in-vitro Cortical Neuronal Cell Survival after Laser Induced Axotomy

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