Monocyte Chemoattractant Protein-1 Plays a Critical Role in Neuroblast Migration after Focal Cerebral Ischemia

Yan, Yonggang; Sailor, Kurt A.; Lang, Bradley T.; Park, Seung Won; Vemuganti, Raghu; Dempsey, Robert J.

doi:10.1038/sj.jcbfm.9600432

Cited by 238 publications

(216 citation statements)

References 40 publications

(63 reference statements)

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“…We have shown before that MMP‐9 and MCP‐1 are reduced in ischemic stroke with post‐stroke BML‐111 administration (Hawkins et al., 2014). These factors are important in neural stem cell proliferation and migration during neurogenesis after ischemic stroke (Lee et al., 2006; L. Wang et al., 2006; Widera et al., 2004; Yan et al., 2007). Additionally, MMP‐9 is important in vascular remodeling after stroke and inhibiting MMP‐9 1 week after stroke increases infarct size and worsens outcomes (Zhao et al., 2006).…”

Section: Discussionmentioning

confidence: 99%

Targeting resolution of neuroinflammation after ischemic stroke with a lipoxin A₄ analog: Protective mechanisms and long‐term effects on neurological recovery

et al. 2017

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BackgroundResolution of inflammation is an emerging new strategy to reduce damage following ischemic stroke. Lipoxin A4 (LXA 4) is an anti‐inflammatory, pro‐resolution lipid mediator that reduces neuroinflammation in stroke. Since LXA 4 is rapidly inactivated, potent analogs have been synthesized, including BML‐111. We hypothesized that post‐ischemic, intravenous treatment with BML‐111 for 1 week would provide neuroprotection and reduce neurobehavioral deficits at 4 weeks after ischemic stroke in rats. Additionally, we investigated the potential protective mechanisms of BML‐111 on the post‐stroke molecular and cellular profile.MethodsA total of 133 male Sprague‐Dawley rats were subjected to 90 min of transient middle cerebral artery occlusion (MCAO) and BML‐111 administration was started at the time of reperfusion. Two methods of week‐long BML‐111 intravenous administration were tested: continuous infusion via ALZET ® osmotic pumps (1.25 and 3.75 μg μl−1 hr−1), or freshly prepared daily single injections (0.3, 1, and 3 mg/kg). We report for the first time on the stability of BML‐111 and characterized an optimal dose and a dosing schedule for the administration of BML‐111.ResultsOne week of BML‐111 intravenous injections did not reduce infarct size or improve behavioral deficits 4 weeks after ischemic stroke. However, post‐ischemic treatment with BML‐111 did elicit early protective effects as demonstrated by a significant reduction in infarct volume and improved sensorimotor function at 1 week after stroke. This protection was associated with reduced pro‐inflammatory cytokine and chemokine levels, decreased M1 CD40+ macrophages, and increased alternatively activated, anti‐inflammatory M2 microglia/macrophage cell populations in the post‐ischemic brain.ConclusionThese data suggest that targeting the endogenous LXA 4 pathway could be a promising therapeutic strategy for the treatment of ischemic stroke. More work is necessary to determine whether a different dosing regimen or more stable LXA 4 analogs could confer long‐term protection.

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Section: Discussionmentioning

confidence: 99%

Targeting resolution of neuroinflammation after ischemic stroke with a lipoxin A₄ analog: Protective mechanisms and long‐term effects on neurological recovery

et al. 2017

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“…We have previously shown that when mutant SOD1 is expressed in rats, the environment around degenerating motor neurons encourages the survival and migration of hNPC releasing GDNF (15). The exact signals released by the damaged brain that encourage stem cell migration and survival remain to be established, although release of growth factors such as IGF-1 or specific chemoattractants from damaged tissues may play a crucial role (35,36). Furthermore, neural stem cells express CXC chemokine receptor 4 (CXCR4) on their surface which may home in to the ligand stromal cell-derived factor 1 alpha that is up regulated in areas of inflammation (10).…”

Section: Discussionmentioning

confidence: 99%

Lesion-Induced Increase in Survival and Migration of Human Neural Progenitor Cells Releasing GDNF

et al. 2008

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The use of human neural progenitor cells (hNPC) has been proposed to provide neuronal replacement or astrocytes delivering growth factors for brain disorders such as Parkinson's and Huntington's disease. Success in such studies likely requires migration from the site of transplantation and integration into host tissue in the face of ongoing damage. In the current study, hNPC modified to release glial cell line derived neurotrophic factor (hNPC GDNF ) were transplanted into either intact or lesioned animals. GDNF release itself had no effect on the survival, migration or differentiation of the cells. The most robust migration and survival was found using a direct lesion of striatum (Huntington's model) with indirect lesions of the dopamine system (Parkinson's model) or intact animals showing successively less migration and survival. No lesion affected differentiation patterns. We conclude that the type of brain injury dictates migration and integration of hNPC which has important consequences when considering transplantation of these cells as a therapy for neurodegenerative diseases.

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“…Chemokine (C-C motif) ligand 2, leukemia inhibitory factor, and tumor necrosis factor (TNF)-α are also inflammatory signaling molecules that are released by astrocytes and microglia/ macrophages after stroke, induce distinct stages of normal neurogenesis, and have been implicated in poststroke neurogenesis [27,31,32]. Activated astrocytes and microglia release other cytokines and chemokines that participate in poststroke neurogenesis [27,30,33].…”

Section: Radial Stroke: Triggers For Neural Repairmentioning

confidence: 99%

The 3 Rs of Stroke Biology: Radial, Relayed, and Regenerative

Carmichael

2016

Neurotherapeutics

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Stroke not only causes initial cell death, but also a limited process of repair and recovery. As an overall biological process, stroke has been most often considered from the perspective of early phases of ischemia, how these inter-relate and lead to expansion of the infarct. However, just as the biology of later stages of stroke becomes better understood, the clinical realities of stroke indicate that it is now more a chronic disease than an acute killer. As an overall biological process, it is now more important to understand how early cell death leads to the later, limited recovery so as develop an integrative view of acute to chronic stroke. This progression from death to repair involves sequential stages of primary cell death, secondary injury events, reactive tissue progenitor responses, and formation of new neuronal circuits. This progression is radial: from the tissue that suffers the infarct secondary injury signals, including free radicals and inflammatory cytokines, radiate out from the stroke core to trigger later regenerative events. Injury and repair processes occur not just in the local stroke site, but are also triggered in the connected networks of neurons that had existed in the stroke center: damage signals are relayed throughout a brain network. From these relayed, distributed damage signals, reactive astrocytosis, inflammatory processes, and the formation of new connections occur in distant brain areas. In short, emerging data in stroke cell death studies and the development of the field of stroke neural repair now indicate a continuum in time and in space of progressive events that can be considered as the 3 Rs of stroke biology: radial, relayed, and regenerative.

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Monocyte Chemoattractant Protein-1 Plays a Critical Role in Neuroblast Migration after Focal Cerebral Ischemia

Cited by 238 publications

References 40 publications

Targeting resolution of neuroinflammation after ischemic stroke with a lipoxin A₄ analog: Protective mechanisms and long‐term effects on neurological recovery

Targeting resolution of neuroinflammation after ischemic stroke with a lipoxin A₄ analog: Protective mechanisms and long‐term effects on neurological recovery

Lesion-Induced Increase in Survival and Migration of Human Neural Progenitor Cells Releasing GDNF

The 3 Rs of Stroke Biology: Radial, Relayed, and Regenerative

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Monocyte Chemoattractant Protein-1 Plays a Critical Role in Neuroblast Migration after Focal Cerebral Ischemia

Cited by 238 publications

References 40 publications

Targeting resolution of neuroinflammation after ischemic stroke with a lipoxin A4 analog: Protective mechanisms and long‐term effects on neurological recovery

Targeting resolution of neuroinflammation after ischemic stroke with a lipoxin A4 analog: Protective mechanisms and long‐term effects on neurological recovery

Lesion-Induced Increase in Survival and Migration of Human Neural Progenitor Cells Releasing GDNF

The 3 Rs of Stroke Biology: Radial, Relayed, and Regenerative

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Targeting resolution of neuroinflammation after ischemic stroke with a lipoxin A₄ analog: Protective mechanisms and long‐term effects on neurological recovery

Targeting resolution of neuroinflammation after ischemic stroke with a lipoxin A₄ analog: Protective mechanisms and long‐term effects on neurological recovery