Stroke and Traumatic Brain Injury

Lerouet, Dominique; Besson, Valérie; Plotkine, Michel

doi:10.1002/9783527679348.ch17

Cited by 2 publications

References 130 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

Neuropharmacology in traumatic brain injury: from preclinical to clinical neuroprotection?

Lerouet

Marchand-Leroux

Besson

2021

Fundamemntal Clinical Pharma

Self Cite

View full text Add to dashboard Cite

Traumatic brain injury (TBI) constitutes a major health problem worldwide and is a leading cause of death and disability in individuals, contributing to devastating socioeconomic consequences. Despite numerous promising pharmacological strategies reported as neuroprotective in preclinical studies, the translation to clinical trials always failed, albeit the great diversity of therapeutic targets evaluated. In this review, first, we described epidemiologic features, causes, and primary and secondary injuries of TBI. Second, we outlined the current literature on animal models of TBI, and we described their goals, their advantages and disadvantages according to the species used, the type of injury induced, and their clinical relevance. Third, we defined the concept of neuroprotection and discussed its evolution. We also identified the reasons that might explain the failure of clinical translation. Then, we reviewed post‐TBI neuroprotective treatments with a focus on the following pleiotropic drugs, considered “low hanging fruit” with high probability of success: glitazones, glibenclamide, statins, erythropoietin, and progesterone, that were largely tested and demonstrated efficient in preclinical models of TBI. Finally, our review stresses the need to establish a close cooperation between basic researchers and clinicians to ensure the best clinical translation for neuroprotective strategies for TBI.

show abstract

Neuropharmacology in traumatic brain injury: from preclinical to clinical neuroprotection?

Lerouet

Marchand-Leroux

Besson

2021

Fundamemntal Clinical Pharma

Self Cite

View full text Add to dashboard Cite

show abstract

Glycine-induced NMDA receptor internalization provides neuroprotection and preserves vasculature following ischemic stroke

Bergeron

Cappelli

Khacho

et al. 2021

Preprint

View full text Add to dashboard Cite

Glycine fulfills several roles in biology including protein synthesis, inhibitory transmission via glycine receptor activation and excitatory transmission through glutamate-sensitive N-methyl-D-aspartate receptors (NMDARs). Low glycine doses enhance NMDAR function while high doses trigger glycine-induced NMDAR internalization (GINI) in vitro. The physiological relevance of GINI has been questioned given that the high-affinity glycine transporter type 1 (GlyT1), located on astrocytes and neurons, maintains synaptic glycine concentrations far below the level that would saturate the glycine binding site (GBS) on NMDARs. Here, we report evidence that GINI occurs also in vivo and is neuroprotective following ischemic insult. Mice pre-treated with a GlyT1 antagonist (GlyT1-A), which increased glycine levels, exhibited smaller stroke volume, reduced cell death, and minimized behavioural deficits following stroke induction by either photothrombosis or endothelin-1. We demonstrate that in a modified in vitro ischemic paradigm, glycine is released at levels surpassing what occurs during ischemia alone. Therefore, glycine accumulates in the synaptic cleft, enhances occupancy of GBS and reaches the set point to trigger GINI. We report that GINI is observed during stroke, in vivo, only in the presence of a GlyT1-A. Moreover, we show evidence of a protective effect on the vasculature in the peri-infarct area. Therefore, these data strongly suggest that GlyT1 is a therapeutic target to prevent cell death following an ischemic event.

show abstract

Stroke and Traumatic Brain Injury

Cited by 2 publications

References 130 publications

Neuropharmacology in traumatic brain injury: from preclinical to clinical neuroprotection?

Neuropharmacology in traumatic brain injury: from preclinical to clinical neuroprotection?

Glycine-induced NMDA receptor internalization provides neuroprotection and preserves vasculature following ischemic stroke

Contact Info

Product

Resources

About