Table 1 Dual roles of astrocyte-derived factors in the BBB integrity after TBI
From: Dual roles of astrocytes in plasticity and reconstruction after traumatic brain injury
Astrocyte-derived factors | Characters | Receptors | Role in BBB post-TBI | Mechanisms | Related agents | Other functions | References |
|---|---|---|---|---|---|---|---|
ANG-1 | Glycoprotein | Tie-2 | Protect | Promote endothelial cells, vascular remodeling, and stability; increase TJ-related proteins | Exogenous ANG-1 or ANG-1 mimetic peptides | Promote angiogenesis; suppress VEGF-induce expression of cell adhesion molecules and leukocyte infiltration | 179-181 |
SHH | Glycoprotein | Patched-1 | Protect | Attenuate endothelial cells apoptosis; increase TJ-related proteins | Exogenous SHH | Promote angiogenesis; promote normal pattern formation and cellular differentiation in the developing CNS; suppress cell adhesion molecules expression and leukocyte infiltration | 182-185 |
GDNF | Neurotrophic factor | GDNF receptor α-1 and -2 | Protect | Increase TJ-related proteins | Exogenous GDNF | Promote the normal postnatal development of BBB, neuronal survival and angiogenesis; axon guidance and synapse formation; control endothelial functions; | 186-188 |
RA | Active metabolite synthesized from retinol by retinaldehyde dehydrogenase | Nuclear RA receptors | Protect | Increase TJ-related proteins and vascular endothelial cadherin | Exogenous RA | Promote growth and development in the CNS; regulate synaptic plasticity; suppress the expression of cell adhesion molecules | 189-191 |
IGF-1 | A member of insulin gene family | IGF-1 receptors | Protect | Attenuate endothelial cells apoptosis | Exogenous IGF-1 | Promote neurogenesis; reduce cell death; support injury repair; regulate synaptic neuroplasticity | 78, 192, 193 |
APOE | A member of the apolipoprotein family | \ | Protect* | Suppress the activity of MMP-9; increase TJ-related proteins | APOE-mimetic peptide COG1410 | Support lipid transport and injury repair | 194-203 |
VEGF | An angiogenetic factor | VEGFR-1 and VEGFR-2 | Damage | Decrease TJ-related proteins | SU5416 (VEGFR-2 inhibitor); cavtratin (a selective inhibitor of VEGF-A) | Promote endothelial proliferation and differentiation for angiogenesis; induce cell adhesion molecules expression and leukocyte infiltration | 204-207 |
MMP | Zinc-endopeptidases | \ | Damage | Enhance endothelial cell apoptosis; degrade TJ-related proteins and ECM molecules | Ro32–3555 (a broad spectrum MMP inhibitor) | Promote angiogenesis; regulate expression of cell adhesion molecules and subsequent leukocyte infiltration | 208, 213, 214 |
NO | A potent vasodilator synthesized from L-arginine by NO synthase | \ | Damage | Enhance MMPs activation; decrease TJ-related proteins; induce apoptosis through cGMP monophosphate-independent pathways, suppress apoptosis through cGMP pathway | Nomega-Nitro-L-arginine methyl ester (a non-specific NOS inhibitor) | Regulate blood flow for neuronal activity; exacerbate inflammatory reaction | 78, 215, 216 |
Glutamate | A major excitatory transmitter and | NMDA receptor and the AMPA receptor | Damage | Induce excessive vascular permeability via activation of NMDA receptors; decrease TJ-related proteins | MK-801 (non-competitive NMDA receptor antagonist); CGS-19755 (competitive NMDA receptor antagonist); NBQX, DNQX (competitive AMPA receptor antagonists)** | Regulate synaptic plasticity and formation; induce vasodilatation; regulate neuronal survival | 208-210 |
ETs | Potent endogenous vasoconstrictors | Endothelin receptor type A/B | Damage | Exacerbate BBB inflammation; enhance MMPs activation; degrade TJ-related proteins | S-0139 (selective ETA receptor antagonist); BQ788 (selective ETB receptor antagonist) | Induce expression of cell adhension molecules; regulate endothelial function | 21, 211, 212 |
S1P | A biologically active lipid | S1PR 1-5 | Dual | Regulate VEGF activation and TJ-related proteins | Siponimod, fingolimod, TASP0277308 (antagonists of S1PR 1); artesunate, isoflurane (agonists of S1PR 1)✝ | Regulate synaptic plasticity | 143, 222-226 |