Post-injury administration of a combination of memantine and 17β-estradiol is protective in a rat model of traumatic brain injury

Day, Nicole L.; Carle, Matthew S.; Floyd, Candace L.

doi:10.1016/j.neuint.2017.04.018

Cited by 14 publications

(6 citation statements)

References 72 publications

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“…Further investigation of the influence of estrogens in models of CNS trauma is an important means of differentiation between hormonally driven effects (i.e., plasticity) and specific patterns of gene expression that are linked to sex chromosome codification (i.e., heterogeneity). 17β-estradiol has been shown to have neuroprotective effects in pre-clinical models of SCI and TBI ( Siriphorn et al, 2012 ; Day et al, 2017 ), and therefore targeted manipulation of estrogen signaling pathways may be a viable therapeutic target.…”

Section: Traumatic Injurymentioning

confidence: 99%

Diversity of Reactive Astrogliosis in CNS Pathology: Heterogeneity or Plasticity?

Moulson

Squair

Franklin

et al. 2021

Front. Cell. Neurosci.

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Astrocytes are essential for the development and homeostatic maintenance of the central nervous system (CNS). They are also critical players in the CNS injury response during which they undergo a process referred to as “reactive astrogliosis.” Diversity in astrocyte morphology and gene expression, as revealed by transcriptional analysis, is well-recognized and has been reported in several CNS pathologies, including ischemic stroke, CNS demyelination, and traumatic injury. This diversity appears unique to the specific pathology, with significant variance across temporal, topographical, age, and sex-specific variables. Despite this, there is limited functional data corroborating this diversity. Furthermore, as reactive astrocytes display significant environmental-dependent plasticity and fate-mapping data on astrocyte subsets in the adult CNS is limited, it remains unclear whether this diversity represents heterogeneity or plasticity. As astrocytes are important for neuronal survival and CNS function post-injury, establishing to what extent this diversity reflects distinct established heterogeneous astrocyte subpopulations vs. environmentally dependent plasticity within established astrocyte subsets will be critical for guiding therapeutic development. To that end, we review the current state of knowledge on astrocyte diversity in the context of three representative CNS pathologies: ischemic stroke, demyelination, and traumatic injury, with the goal of identifying key limitations in our current knowledge and suggesting future areas of research needed to address them. We suggest that the majority of identified astrocyte diversity in CNS pathologies to date represents plasticity in response to dynamically changing post-injury environments as opposed to heterogeneity, an important consideration for the understanding of disease pathogenesis and the development of therapeutic interventions.

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Section: Traumatic Injurymentioning

confidence: 99%

Diversity of Reactive Astrogliosis in CNS Pathology: Heterogeneity or Plasticity?

Moulson

Squair

Franklin

et al. 2021

Front. Cell. Neurosci.

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“…Several clinical studies have demonstrated that males have higher mortality rates and higher incidence of complications than females [10][11][12], suggesting that gonadal steroids such as 17β-estradiol (E2) play a critical role in the outcome of TBI. Animal studies have demonstrated the remarkable neuroprotective potential of E2 [13][14][15][16]. However, clinical trials have shown conflicting results regarding the effectiveness of female sexual hormones in TBI treatment [17,18].…”

Section: Introductionmentioning

confidence: 99%

The Role of Estradiol in Traumatic Brain Injury: Mechanism and Treatment Potential

Kövesdi

Szabó-Meleg

Ábrahám

2020

IJMS

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Patients surviving traumatic brain injury (TBI) face numerous neurological and neuropsychological problems significantly affecting their quality of life. Extensive studies over the past decades have investigated pharmacological treatment options in different animal models, targeting various pathological consequences of TBI. Sex and gender are known to influence the outcome of TBI in animal models and in patients, respectively. Apart from its well-known effects on reproduction, 17β-estradiol (E2) has a neuroprotective role in brain injury. Hence, in this review, we focus on the effect of E2 in TBI in humans and animals. First, we discuss the clinical classification and pathomechanism of TBI, the research in animal models, and the neuroprotective role of E2. Based on the results of animal studies and clinical trials, we discuss possible E2 targets from early to late events in the pathomechanism of TBI, including neuroinflammation and possible disturbances of the endocrine system. Finally, the potential relevance of selective estrogenic compounds in the treatment of TBI will be discussed.

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“…Free radical scavenging antioxidant agents such as lipoic acid and DHA in combination with anti-inflammatory medications including curcumin have been used as an adjunct to neural stem cell grafting, with positive effects on cell graft survivial and neuronal differentiation [51][52][53]. Combinations of NMDA receptor antagonist anti-excitatory medications such as memantine and endogenous hormones including estrogen have been shown to reduce neuronal death in preclinical models [54,55]. In clinical trials the combination of the anti-excitatory GABA agonist propofol and the opioid fentanyl led to significant reductions in ICP, however long-term outcomes were not reported [56].…”

Section: Combined Multitarget Pharmacologic Therapiesmentioning

confidence: 99%

Multi-mechanistic Approaches to the Treatment of Traumatic Brain Injury: A Review

Lynch¹,

Narayan²,

Li³

2023

Preprint

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Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Despite extensive research efforts, the majority of trialed monotherapies to date have failed to demonstrate significant benefit. It has been suggested that this is due to the complex pathophysiology of TBI, which may possibly be addressed by a combination of therapeutic interventions. In this article, we have reviewed combinations of different pharmacologic treatments, combinations of non-pharmacologic interventions, and combined pharmacologic and non-pharmacologic interventions for TBI. Both preclinical and clinical studies have been included. While promising results have been found in animal models, clinical trials of combination therapies have not yet shown clear benefit. This may possibly be due to their application without consideration of the evolving pathophysiology of TBI. Improvements of this paradigm may come from novel interventions guided by multimodal neuromonitoring and multimodal imaging techniques, as well as the application of multi-targeted non-pharmacologic and endogenous therapies. There also needs to be a greater representation of female subjects in preclinical and clinical studies.

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Post-injury administration of a combination of memantine and 17β-estradiol is protective in a rat model of traumatic brain injury

Cited by 14 publications

References 72 publications

Diversity of Reactive Astrogliosis in CNS Pathology: Heterogeneity or Plasticity?

Diversity of Reactive Astrogliosis in CNS Pathology: Heterogeneity or Plasticity?

The Role of Estradiol in Traumatic Brain Injury: Mechanism and Treatment Potential

Multi-mechanistic Approaches to the Treatment of Traumatic Brain Injury: A Review

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