Retinoic Acid Modulation in Cerebral Ischemia

Retinoic acid, an active metabolite of vitamin A, has emerged as a multifaceted agent in the context of cerebral ischemia, where insufficient blood flow precipitates neuronal injury and functional deficits. Through binding to nuclear retinoic acid receptors, it regulates gene networks that underpin neuronal survival, differentiation and repair. Experimental studies have demonstrated that retinoic acid attenuates oxidative stress and inflammatory responses in the ischaemic cortex, in part by modulating microglial and astrocyte activation and suppressing pro-inflammatory cytokines. Concurrently, it promotes anti-apoptotic signalling via the PI3K-Akt cascade, stabilises interactions among Bcl-2 family proteins and limits caspase activation. At the level of protein homeostasis, retinoic acid has been shown to preserve ubiquitin–proteasome components that are downregulated after ischaemic insult. Moreover, it supports endogenous neurorepair by enhancing neuroprogenitor proliferation and migration within the subventricular zone and by upregulating growth-associated proteins that foster axonal regrowth. Together, these actions converge on improved neurological outcomes and reduced infarct volumes in animal models, highlighting retinoic acid’s promise as a therapeutic modulator of post-ischaemic injury and repair.

Research from Nature Portfolio

Delayed intranasal administration of 9-cis retinoic acid following middle cerebral artery occlusion in rodents has been shown to elevate cerebral retinoic acid levels and substantially enhance motor recovery. This treatment stimulated proliferation and outward migration of subventricular zone neuroprogenitors into the peri-infarct cortex, as evidenced by increased incorporation of proliferation markers and augmented neurosphere formation in vitro. The study supports a non-invasive, time-flexible approach to harness endogenous repair mechanisms and underscores the capacity of retinoic acid to facilitate both functional restoration and structural remodelling after stroke.

Retinoic Acid Modulation in Cerebral Ischemia publication trend

The graph below shows the total number of articles in retinoic acid modulation in cerebral ischemia across all publications each year (not limited to Nature Index journals).

Technical terms

Retinoic acid: A vitamin A derivative that regulates gene expression through nuclear receptors.

Cerebral ischemia: A pathological condition in which blood flow to the brain is insufficient to meet metabolic demands.

Neurogenesis: The process by which new neurons are generated from progenitor cells.

Apoptosis: Programmed cell death characterised by caspase activation and DNA fragmentation.

Glial cells: Non-neuronal support cells in the central nervous system, including astrocytes and microglia.

PI3K-Akt signalling: A intracellular pathway that promotes cell survival and growth.

Ubiquitin–proteasome system: A cellular mechanism for targeted protein degradation and turnover.

References

1. Effects of retinoic acid on ischemic brain injury-induced neurogenesis. Experimental & Molecular Medicine (2007).
2. 9-cis retinoic acid induces neurorepair in stroke brain. Scientific Reports (2017).
3. Retinoic acid protects from experimental cerebral infarction by upregulating GAP-43 expression. Brazilian Journal of Medical and Biological Research (2017).
4. Retinoic acid regulates the ubiquitin–proteasome system in a middle cerebral artery occlusion animal model. Laboratory Animal Research (2022).
5. Retinoic acid alleviates the reduction of Akt and Bad phosphorylation and regulates Bcl-2 family protein interactions in animal models of ischemic stroke. PLOS ONE (2024).
6. Retinoic acid attenuates ischemic injury-induced activation of glial cells and inflammatory factors in a rat stroke model. PLOS ONE (2024).