Retinoic acid protects from experimental cerebral infarction by upregulating GAP-43 expression

Li, Y.; Gao, Xiang; Wang, Q.; Yang, Yun; Liu, H.; Zhang, B.; Li, L.

doi:10.1590/1414-431x20175561

Cited by 11 publications

(7 citation statements)

References 41 publications

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“…GAP-43 immunostaining was used as a surrogate measure of axon growth and/or terminal sprouting in stroke models [ 37 ]. Immunohistochemical staining in the present study showed that GAP-43 remarkably increased at 3 d, continued until 7 d, and decreased from 14 d to 28 d after MCAO, which corresponded fairly closely with previous studies [ 38 , 39 ]. Our data provided evidence of a dynamic process of axon growth and regeneration.…”

Section: Discussionsupporting

confidence: 93%

Effect of Tetramethylpyrazine on Neuroplasticity after Transient Focal Cerebral Ischemia Reperfusion in Rats

Lin

Hao

Gong

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Tetramethylpyrazine (TMP) has been widely used in ischemic stroke in China. The regulation of neuroplasticity may underlie the recovery of some neurological functions in ischemic stroke. Middle cerebral artery occlusion (MCAO) model was established in this study. Rats were divided into three groups: sham group, model group, and TMP group. The neurological function was evaluated using modified neurological severity score (mNSS). Following the neurological function test, expression of synaptophysin (SYP) and growth-associated protein 43 (GAP-43) were analyzed through immunohistochemistry at 3 d, 7 d, 14 d, and 28 d after MCAO. Finally, the synaptic structural plasticity was investigated using transmission electron microscopy (TEM). The TMP group showed better neurological function comparing to the model group. SYP levels increased gradually in ischemic penumbra (IP) in the model group and could be enhanced by TMP treatment at 7 d, 14 d, and 28 d, whereas GAP-43 levels increased from 3 d to 7 d and thereafter decreased gradually from 14 d to 28 d in the model group, which showed no significant improvement in the TMP group. The results of TEM showed a flatter synaptic interface, a thinner postsynaptic density (PSD), and a wider synaptic cleft in the model group, and the first two alterations could be ameliorated by TMP. Then, a Pearson’s correlation test revealed mNSS markedly correlated with SYP and synaptic ultrastructures. Taken together, TMP is capable of promoting functional outcome after ischemic stroke, and the mechanisms may be partially associated with regulation of neuroplasticity.

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Section: Discussionsupporting

confidence: 93%

Effect of Tetramethylpyrazine on Neuroplasticity after Transient Focal Cerebral Ischemia Reperfusion in Rats

Lin

Hao

Gong

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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“…Interestingly, pre‐injury administration of ATRA reduced infarction volume after experimental stroke and improved neurological outcome and integrity of the BBB (Li et al, 2017, 2018). To some degree, the beneficial effects of ATRA have been attributed to its anti‐inflammatory actions (Behairi et al, 2016; Choi et al, 2009; Theus, Sparks, Liao, Ren, & Luo, 2017).…”

Section: Introductionmentioning

confidence: 99%

Administration of all‐trans retinoic acid after experimental traumatic brain injury is brain protective

Hummel

Ulbrich

Appel

et al. 2020

British J Pharmacology

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Background and Purpose: All-trans retinoic acid (ATRA) is a vitamin A metabolite, important in the developing and mature brain. Pre-injury ATRA administration ameliorates ischaemic brain insults in rodents. This study examined the effects of posttraumatic ATRA treatment in experimental traumatic brain injury (TBI). Experimental Approach: Male adult mice were subjected to the controlled cortical impact model of TBI or sham procedure and killed at 7 or 30 days post-injury (dpi). ATRA (10 mg kg−1, i.p.) was given immediately after the injury and 1, 2 and 3 dpi. Neurological function and sensorimotor coordination were evaluated. Brains were processed for (immuno-) histological, mRNA and protein analyses (qPCR and western blot). Key Results: ATRA treatment reduced brain lesion size, reactive astrogliosis and axonal injury at 7 dpi, and hippocampal granule cell layer (GCL) integrity was protected at 7 and 30 dpi, independent of cell proliferation in neurogenic niches and bloodbrain barrier damage. Neurological and motor deficits over time and the brain tissue loss at 30 dpi were not affected by ATRA treatment. ATRA decreased gene expression of markers for damage-associated molecular pattern (HMGB1), apoptosis (caspase-3 and Bax), activated microglia (TSPO), and reactive astrogliosis (GFAP, SerpinA3N) at 7 dpi and a subset of markers at 30 dpi (TSPO, GFAP). Conclusion and Implications: In experimental TBI, post-traumatic ATRA administration exerted brain protective effects, including long-term protection of GCL integrity, but did not affect neurological and motor deficits. Further investigations are required to optimize treatment regimens to enhance ATRA's brain protective effects and improve outcomes.

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“…Modulating post-stroke neural inflammation has been suggested as an important therapeutic strategy in cerebral ischemia [32]. All-trans retinoic acid is a well-established inflammatory modulator which has raised interest in the field of stroke therapy [9, 10, 33–35]. The current study demonstrates that atRA prophylactic treatment modulates post-stroke neural inflammation through regulation of neutrophil functions.…”

Section: Discussionmentioning

confidence: 65%

“…All-trans retinoic acid (atRA) is the ligand of retinoic acid receptors (RARs) and displays potent immunoregulatory effects on autoimmune diseases [3–8]. Recent studies have documented that prophylactic administration of atRA reduced brain injury in stroke as neuronal viability and blood-brain barrier (BBB) integrity were improved and glia cell activation was controlled [9–11]. Nevertheless, the underlying mechanisms of the protection offered by atRA remain to be elusive.…”

Section: Introductionmentioning

confidence: 99%

All trans-retinoic acid protects against acute ischemic stroke by modulating neutrophil functions through STAT1 signaling

Cai

Wang

et al. 2019

J Neuroinflammation

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Background and purpose Regulation of neural inflammation is considered as a vital therapeutic target in ischemic stroke. All-trans retinoic acid (atRA), a potent immune modulator, has raised interest in the field of stroke therapy. However, the immunological mechanisms for atRA-mediated neuroprotection remain elusive. The current study evaluated the impact of atRA on post-stroke neural inflammation and elucidated the mechanisms involved in the regulation of related neutrophil functions. Methods atRA was prophylactically administered to mice 1 day before transient middle cerebral artery occlusion (tMCAO, 1 h) and repeated daily immediately after reperfusion for 3 days. Stroke outcomes, neutrophil polarization, and formation of neutrophil extracellular traps (NETs) in the stroke lesion were assessed. Neutrophil depletion was induced with anti-Ly6G antibodies. Primary neutrophil cultures were used to explore the mechanisms of atRA treatment. Results Prophylactic atRA treatment reduced infarct volumes and neurological deficits at 1 day after tMCAO. Post-stroke neural inflammation was attenuated and neutrophil accumulation in lesion was downregulated. atRA treatment skewed neutrophil toward N2 phenotype which facilitated its clearance by macrophage and inhibited NETs formation. The functions of neutrophil were indispensable in the protective effects of atRA and were associated with suppression to STAT1 signaling by atRA. Administration of atRA after stroke still provided efficient protection to cerebral ischemia. Conclusion atRA displays potent therapeutic efficacy in ischemic stroke by attenuating neural inflammation. Treatment of atRA impeded neutrophil accumulation, favored N2 polarization, and forbade NETs formation in ischemic lesion. STAT1 signaling played a decisive role in the mechanisms of atRA-afforded regulation to neutrophil. Electronic supplementary material The online version of this article (10.1186/s12974-019-1557-6) contains supplementary material, which is available to authorized users.

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Retinoic acid protects from experimental cerebral infarction by upregulating GAP-43 expression

Cited by 11 publications

References 41 publications

Effect of Tetramethylpyrazine on Neuroplasticity after Transient Focal Cerebral Ischemia Reperfusion in Rats

Effect of Tetramethylpyrazine on Neuroplasticity after Transient Focal Cerebral Ischemia Reperfusion in Rats

Administration of all‐trans retinoic acid after experimental traumatic brain injury is brain protective

All trans-retinoic acid protects against acute ischemic stroke by modulating neutrophil functions through STAT1 signaling

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