The upregulation of annexin A2 after spinal cord injury in rats may have implication for astrocyte proliferation

Chen, Jiajia; Cui, Zhiming; Yang, Saishuai; Wu, Chunshuai; Li, Weidong; Bao, Guofeng; Xu, Guanhua; Sun, Yuyu; Wang, Lingling; Zhang, Jinlong

doi:10.1016/j.npep.2016.10.007

Cited by 21 publications

(10 citation statements)

References 35 publications

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“…We found a significant increase of AnxA2 expression at three days after TBI in the ipsilateral brain. Consistently, an earlier study reported that AnxA2 expression was increased after traumatic spinal cord injury [17]. The most important finding of the present study is the association of AnxA2 deficiency with the increased leukocyte brain infiltration, which is consistent with previous studies showing that A2KO mice exhibit increased pulmonary neutrophil infiltration in polymicrobial sepsis models [14] as well as in response to subacute alveolar hypoxia [18] compared to WT mice.…”

Section: Discussionsupporting

confidence: 93%

Annexin A2 Deficiency Exacerbates Neuroinflammation and Long-Term Neurological Deficits after Traumatic Brain Injury in Mice

Liu

Jiang

Chung

et al. 2019

IJMS

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Our laboratory and others previously showed that Annexin A2 knockout (A2KO) mice had impaired blood–brain barrier (BBB) development and elevated pro-inflammatory response in macrophages, implying that Annexin A2 (AnxA2) might be one of the key endogenous factors for maintaining homeostasis of the neurovascular unit in the brain. Traumatic brain injury (TBI) is an important cause of disability and mortality worldwide, and neurovascular inflammation plays an important role in the TBI pathophysiology. In the present study, we aimed to test the hypothesis that A2KO promotes pro-inflammatory response in the brain and worsens neurobehavioral outcomes after TBI. TBI was conducted by a controlled cortical impact (CCI) device in mice. Our experimental results showed AnxA2 expression was significantly up-regulated in response to TBI at day three post-TBI. We also found more production of pro-inflammatory cytokines in the A2KO mouse brain, while there was a significant increase of inflammatory adhesion molecules mRNA expression in isolated cerebral micro-vessels of A2KO mice compared with wild-type (WT) mice. Consistently, the A2KO mice brains had a significant increase in leukocyte brain infiltration at two days after TBI. Importantly, A2KO mice had significantly worse sensorimotor and cognitive function deficits up to 28 days after TBI and significantly larger brain tissue loss. Therefore, these results suggested that AnxA2 deficiency results in exacerbated early neurovascular pro-inflammation, which leads to a worse long-term neurologic outcome after TBI.

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Section: Discussionsupporting

confidence: 93%

Annexin A2 Deficiency Exacerbates Neuroinflammation and Long-Term Neurological Deficits after Traumatic Brain Injury in Mice

Liu

Jiang

Chung

et al. 2019

IJMS

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“…In agreement with previous reports [5,39], we also confirmed that LPS induced neurotrophic A2 astrocytes because they were double-positive to S100A10 and GFAP, suggesting the activation of anti-inflammatory mechanisms. Accordingly, after LPS stimulation, S100A10 protein in complex with the Ca 2+ /lipid-binding protein annexin A2 (annexin A2-S100A10 complex) [40] inhibits astrocytic proliferation and modulates inflammasome activation as well as cytokines released in the CNS [41]. However, the detrimental effect of LPS prevailed despite neurotrophic A2 astrocytes, as shown here and by others [14,28,42], thus indicating that the endogenous neurotrophic mechanism needs further reinforcement to overcome the neurotoxic effect of A1 astrocytes [16,43,44].…”

Section: Discussionmentioning

confidence: 50%

LPS Triggers Acute Neuroinflammation and Parkinsonism Involving NLRP3 Inflammasome Pathway and Mitochondrial CI Dysfunction in the Rat

Valenzuela-Arzeta

Soto-Rojas

Flores-Martínez

et al. 2023

IJMS

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Whether neuroinflammation leads to dopaminergic nigrostriatal system neurodegeneration is controversial. We addressed this issue by inducing acute neuroinflammation in the substantia nigra (SN) with a single local administration (5 µg/2 µL saline solution) of lipopolysaccharide (LPS). Neuroinflammatory variables were assessed from 48 h to 30 days after the injury by immunostaining for activated microglia (Iba-1 +), neurotoxic A1 astrocytes (C3 + and GFAP +), and active caspase-1. We also evaluated NLRP3 activation and Il-1β levels by western blot and mitochondrial complex I (CI) activity. Fever and sickness behavior was assessed for 24 h, and motor behavior deficits were followed up until day 30. On this day, we evaluated the cellular senescence marker β-galactosidase (β-Gal) in the SN and tyrosine hydroxylase (TH) in the SN and striatum. After LPS injection, Iba-1 (+), C3 (+), and S100A10 (+) cells were maximally present at 48 h and reached basal levels on day 30. NLRP3 activation occurred at 24 h and was followed by a rise of active caspase-1 (+), Il-1β, and decreased mitochondrial CI activity until 48 h. A significant loss of nigral TH (+) cells and striatal terminals was associated with motor deficits on day 30. The remaining TH (+) cells were β-Gal (+), suggesting senescent dopaminergic neurons. All the histopathological changes also appeared on the contralateral side. Our results show that unilaterally LPS-induced neuroinflammation can cause bilateral neurodegeneration of the nigrostriatal dopaminergic system and are relevant for understanding Parkinson’s disease (PD) neuropathology.

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“…Intriguingly, our combinatorial analyses of proteome, phosphoproteome and transcriptome of I/R mouse hippocampi revealed that Anxa2 was highly correlation to in ammation responses during I/R. Some studies have demonstrated that Anxa2 is involved in several immune in ammation responses to various injuries, including spinal cord injury, and traumatic brain injury 35,36,75 . However, the opposite function of Anxa2 in in ammatory responses has also been reported.…”

Section: Discussionmentioning

confidence: 93%

Microglial Annexin A2 Deficiency Supresses Inflammatory Response to Alleviate Ischemia Reperfusion-Induced Cerebral Injury

Tian

Yang

Zhang

et al. 2023

Preprint

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Cerebral stroke is one of the leading causes of mortality and disability worldwide. Cerebral ischemia followed by reperfusion (I/R) triggers inflammatory responses, apoptosis, neuronal damage, and even death, while the molecular and cellular mechanisms of neuronal injury caused by cerebral I/R are not fully understood. Here, we integrated proteome, phosphoproteome and transcriptome profile analyses in mouse hippocampiafter I/Rand revealed that the differentially expressed genes (DEGs) and proteins (DEPs) mainly fall into several immune response-related events. Among 11 common DEGs/DEPs, we identified Annexin A2 (Anxa2) was exclusively up-regulated and translocated to membrane in microglial cells in response to oxygen-glucose deprivation followed by reoxygenation (OGD/R). Microglial Anxa2 knockdown suppressed M1- and promoted M2-microglia polarization induced by OGD/R, facilitated nuclear translocation of NF-κB p65 subunit, activated NF-κB transcriptional activity in response to OGD/R, suppressed the expression of OGD/R-induced pro-inflammatory factors including TNF-a, IL-1β, and IL-6, and reduced cell apoptosis in microglial BV2 cells. The conditional medium derived from Anxa2 knockdown-BV2 cell cultures with OGD/R treatment alleviated OGD/R induced-neuronal death . Our findings revealed that microglia Anxa2 plays a critical role in ischemia cerebral injury through inflammatory responses in a cell non-autonomous manner, which might be a potential target for the neuroprotection against I/R cerebral injury.

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The upregulation of annexin A2 after spinal cord injury in rats may have implication for astrocyte proliferation

Cited by 21 publications

References 35 publications

Annexin A2 Deficiency Exacerbates Neuroinflammation and Long-Term Neurological Deficits after Traumatic Brain Injury in Mice

Annexin A2 Deficiency Exacerbates Neuroinflammation and Long-Term Neurological Deficits after Traumatic Brain Injury in Mice

LPS Triggers Acute Neuroinflammation and Parkinsonism Involving NLRP3 Inflammasome Pathway and Mitochondrial CI Dysfunction in the Rat

Microglial Annexin A2 Deficiency Supresses Inflammatory Response to Alleviate Ischemia Reperfusion-Induced Cerebral Injury

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