ArticleBrain research bulletin2015
High therapeutic potential of positive allosteric modulation of α7 nAChRs in a rat model of traumatic brain injury: proof-of-concept.
Article in Brain research bulletin, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 33 citations in OpenAlex.
- Enhancing cognitive recovery in chronic traumatic brain injury through simultaneous allosteric modulation of α7 nicotinic acetylcholine and α5 GABAExperimental neurology · 2024Article
- Non-neuronal cholinergic system in the heart influences its homeostasis and an extra-cardiac site, the blood-brain barrier.Frontiers in cardiovascular medicine · 2024Review
- The role of astrocytic α7 nicotinic acetylcholine receptors in Alzheimer disease.Nature reviews. Neurology · 2023Review
- Pulsed Electromagnetic Fields Protect Against Brain Ischemia by Modulating the Astrocytic Cholinergic Anti-inflammatory Pathway.Cellular and molecular neurobiology · 2023Article
- Agonism of the αExperimental neurology · 2021Article
- Systemic Administration of α7-Nicotinic Acetylcholine Receptor Ligands Does Not Improve Renal Injury or Behavior in Mice With Advanced Systemic Lupus Erythematosus.Frontiers in medicine · 2021Article
- Allosterism of Nicotinic Acetylcholine Receptors: Therapeutic Potential for Neuroinflammation Underlying Brain Trauma and Degenerative Disorders.International journal of molecular sciences · 2020Review
- In Vitro and In Vivo Characterization of Dibenzothiophene Derivatives [Molecules (Basel, Switzerland) · 2020Article
- Article
- Positive Allosteric Modulation of Alpha7 Nicotinic Acetylcholine Receptors Transiently Improves Memory but Aggravates Inflammation in LPS-Treated Mice.Frontiers in aging neuroscience · 2019Article
- Treatment duration affects cytoprotective efficacy of positive allosteric modulation of α7 nAChRs after focal ischemia in rats.Pharmacological research · 2018Article
- Post-Injury Administration of Galantamine Reduces Traumatic Brain Injury Pathology and Improves Outcome.Journal of neurotrauma · 2018Article
- Insights Into Nicotinic Receptor Signaling in Nicotine Addiction: Implications for Prevention and Treatment.Current neuropharmacology · 2018Review
- Cholinergic modulation of the immune system presents new approaches for treating inflammation.Pharmacology & therapeutics · 2017Review
- Therapeutic potential of α7 nicotinic receptor agonists to regulate neuroinflammation in neurodegenerative diseases.Neural regeneration research · 2017Review
- Boosting Endogenous Resistance of Brain to Ischemia.Molecular neurobiology · 2017Article
- Modulatory effects of α7 nAChRs on the immune system and its relevance for CNS disorders.Cellular and molecular life sciences : CMLS · 2016Review
- Development of [(18)F]ASEM, a specific radiotracer for quantification of the α7-nAChR with positron-emission tomography.Biochemical pharmacology · 2015Review
- Rehabilitative Success After Brain Trauma by Augmenting a Subtherapeutic Dose of Environmental Enrichment With Galantamine.Neurorehabilitation and neural repairArticle
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Authors and funding
3 authors at 3 institutions in 1 country.
Funding
Abstract
There are currently no clinically efficacious drug therapies to treat brain damage secondary to traumatic brain injury (TBI). In this proof-of-concept study, we used a controlled cortical impact model of TBI in young adult rats to explore a novel promising approach that utilizes PNU-120596, a previously reported highly selective Type-II positive allosteric modulator (α7-PAM) of α7 nicotinic acetylcholine receptors (nAChRs). α7-PAMs enhance and prolong α7 nAChR activation, but do not activate α7 nAChRs when administered without an agonist. The rational basis for the use of an α7-PAM as a post-TBI treatment is tripartite and arises from: (1) the intrinsic ability of brain injury to elevate extracellular levels of choline (a ubiquitous cell membrane-building material and a selective endogenous agonist of α7 nAChRs) due to the breakdown of cell membranes near the site and time of injury; (2) the ubiquitous expression of functional α7 nAChRs in neuronal and glial/immune brain cells; and (3) the potent neuroprotective and anti-inflammatory effects of α7 nAChR activation. Therefore, both neuroprotective and anti-inflammatory effects can be achieved post-TBI by targeting only a single player (i.e., the α7 nAChR) using α7-PAMs to enhance the activation of α7 nAChRs by injury-elevated extracellular choline. Our data support this hypothesis and demonstrate that subcutaneous administration of PNU-120596 post-TBI in young adult rats significantly reduces both brain cell damage and reactive gliosis. Therefore, our results introduce post-TBI systemic administration of α7-PAMs as a promising therapeutic intervention that could significantly restrict brain injury post-TBI and facilitate recovery of TBI patients.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.