From: Neutrophils in traumatic brain injury (TBI): friend or foe?
Name | Effects | References |
---|---|---|
IL-1α | #IL-1α expression is closely associated with areas of BBB breakdown and neuronal death at stage of injury &Induces angiogenesis in brain endothelial cells | |
IL-1β | #Localizes with the area of neurons loss and might induce neurons death directly <Induces astrocytes to secret hemolymphopoietic cytokines (IL-6, IL-8) | |
IL-3 | &Suppresses secondary degeneration caused by TBI | [213] |
IL-4 | &Induces M2-polarization of microglia or macrophages &Promotes white matter integrity and long-term neurological recovery | |
IL-6 | &Triggers nerve growth factor production in astrocytes <Might be a prognosis marker of TBI patient | |
IL-7 | <Contributes to injury-induced reactive gliosis | [216] |
IL-9 | #Exacerbates excitotoxic brain damage | [217] |
IL-10 | &IL-10 in traumatic brain and CSF both increases significantly during the first days and may downregulate pro-inflammatory cytokines following traumatic brain damage. | [25] |
IL-12 | #Highly increased in nonsurvival TBI patients | [215] |
IL-16 | <Activates microglia and lymphocytes <Promotes activated microglia and lymphocytes accumulated in microvessels | [218] |
IL-17 | <Promotes neutrophils invasion | [219] |
IL-18 | <Peaks at 7 to 14Â days after injury and might participate in delayed neuroinflammation #Induces brain injury in caspase-1-dependent manner <Induces neutrophils themselves to secrete inflammatory related cytokines | |
IL-23 | #Leads to brain damage and neurological deficits | [222] |
CXCL1 | <Recruits circulating-neutrophils into injured brain | |
CXCL2 | <Peaks at 4Â h after TBI, chemotactic for polymorph nuclear leukocytes | |
CXCL3 | <Promotes neutrophils to migrate across epithelial barriers | [61] |
CXCL4 | <Induces macrophage to differentiate into a unique phenotype | |
CXCL5 | #Increases microglia activation as well as BBB damage #Jeopardizes myelination and promotes astrogliosis | [227] |
CXCL8 | <Promotes neutrophils to infiltrate into brain parenchyma | [228] |
CXCL9 | <Promotes lymphocytes to collaborate with mesenchymal stem cells to inhibit T cells’ functions | [229] |
CXCL10 | <Promotes blood-derived monocytes to accumulate around perivascular vessels | |
CXCL11 | &Promotes regenerative processes | [230] |
CCL2 | <Promotes macrophage to infiltrate into parenchyma <Peaks at 8–12 h after TBI <Induces transmigration of monocytes and macrophages across BBB <Activates and induces chemotaxis of T cells and monocytes | |
CCL3 | <Peaks at 4Â h after injury <Activates and induces chemotaxis of T cells and monocytes <Recruits CCR2-positive leukocytes to injured brain | |
CCL4 | <Activates and induces chemotaxis of T cells and monocytes | [232] |
CCL17 | <Participates in leukocytes recruitment | [234] |
CCL22 | <Participates in leukocytes recruitment | [234] |
G-CSF | &Anti-inflammatory <Promotes myeloid differentiation and M-CSF secretion <Reduces T cells’ infiltration &Prolongs neuronal survival | |
M-CSF | #Promotes microglia activation | |
GM-CSF | &Suppresses secondary degeneration caused by TBI | [213] |
HGF | &Promotes survival reconstruction of specific neurons in response to cerebral injury | [176] |
TGF-α | &Induces proliferation, migration, and differentiation of neural stem cells after neurons damage | [238] |
TGF-β | &Down-modulates cellular activation &Blocks inflammatory responses &Plays a role in nerve regeneration by stimulating nerve growth factor production as well as controlling the astrocytosis and scar formation after injury | |
VEGF | &Promotes angiogenesis as well as brain plasticity &Increases the expression of BDNF in brain endothelial cells #Enhance the leakage of BBB | |
Prokineticin 2 | &Participates in constitutive and injury-induced neurogenesis #Might promote over-inflammation | |
TNF-α | #Induces astrocytes to secret hemolymphopoietic cytokines (IL-6, IL-8) #Mediates PMN-driven neurotoxicity directly <Early pro-apoptotic effect in neutrophils | |
Arginase | &Anti-inflammation &Augments neurite growth | [26] |
BDNF | &Increases cell proliferation &Upregulates expression of growth factors and induces neurogenesis | |
Midkine | &Inhibits apoptosis of neurons &Promotes neurite extension | |
Oncostatin M | #Induces the expression of IL-6 and MMPs &Protects neurons from excitotoxic injury | |
NGF | &Supports neurons survival and nerve growth | |
NT4 | &Prevents neuronal cell death after TBI | |
ROS | #Enhances BBB dysfunction #Participates in brain energy perturbation (glucose, lactate glycerol) #Leads to neurons cell death #Induces microglia activation | |
iNOS | <Leads to vasodilatation of blood vessel and improve microcirculation after TBI &Works as an endogenous antioxidant <Contributes to protein nitrosylation and nitration | |
MMP9 | #Breaks down the integrity of BBB <Promotes infiltration of neutrophils &Participates in vessel remodeling and angiogenesis #Mediates PMN-driven neurotoxicity directly | |
MPO | <Reflects the infiltration of neutrophils in brain tissue | [189] |
Cathepsins | #Contributes to TBI-induced cell death through the programmed cell necrosis and mitochondria-mediated apoptotic pathways | [252] |
Defensins | #Penetrates a considerable distance to disrupt the BBB sites | [120] |
Cathelicidin | <Attracts peripheral blood neutrophils, monocytes, and T cells <Promotes IL-1β processing and release | |
NE | #Causes cellular stress (astrocytes and microglia) in the injured brain #Induces acute neurons death |