Table 2.
The mechanisms of cerebral edema and the various anti-edema agents.
| Type of cerebral edema | The affected site and features | Ion channel, transporters, or target | Agents |
|---|---|---|---|
| Cytotoxic edema | All CNS cell types. Especially the astrocytes. Ions and water flow into the cells. The cells swelled. An ion concentration gradient is formed between the capillaries and the brain parenchyma. | Sur1-Trpm4 channel | Oral glibenclamide, Intravenous glibenclamide (RP-1127, BIIB093), Glimepiride, Resveratrol |
| NKCC1 | Bumetanide, ZT-1a | ||
| Aquaporin-4 | Thyroid hormone (T3), Inhaled H2S, Acetazolamide, Lactosides B, Mitochondrial aldehyde dehydrogenase 2, Paeoniflorin and astragaloside IV, Tongxinluo | ||
| Aquaporin-1 | Fullerenol | ||
| Na+/H+ exchanger | HOE-642, Compound RU-1355 | ||
| Ionic edema | Endothelial cells. Ions and water flow into the brain parenchyma from the blood vessels. In this process, the blood-brain barrier remains intact, and a variety of ion channels and transport proteins participate in it. | Sur1-Trpm4 channel | Oral glibenclamide, Intravenous glibenclamide (RP-1127, BIIB093), Glimepiride, Resveratrol |
| NKCC1 | Bumetanide, ZT-1a | ||
| Na+/H+ exchanger | HOE-642, Compound RU-1355 | ||
| Aquaporin-4 | Thyroid hormone (T3), Inhaled H2S, Acetazolamide, Lactosides B, Mitochondrial aldehyde dehydrogenase 2, Paeoniflorin and astragaloside IV, Tongxinluo | ||
| Aquaporin-1 | Fullerenol | ||
| Vasogenic edema | BBB. | VEGF# | RB-222, Hypertonic saline, VEGF# |
| The integrity of the blood-brain barrier is destroyed, and plasma proteins and water penetrate into the brain tissue | BBB | Alpha-tocopherol, 8-methoxypsoralen, 3-aminobenzamide, Anti-miR-1 or MicroRNA-1 antagomir, MicroRNA-132, MicroRNA-1906, Chemokine-like factors, Magnesium sulfate, Ulinastatin, Ginkgo diterpene lactone meglumine injection, Olaparib, Recombinant human erythropoietin, 1-trifuoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea. | |
| Na+-Ca2+ exchanger | SEA0400 | ||
| Aquaporin-4 | Aquaporin-4# | ||
| Mast cell | Sodium cromoglycate, Intravenous immunoglobulin |
CNS, central nervous system; NKCC1, Na+-K+-2Cl− cotransporter-1; ZT-1a, a highly effective and selective SPAK inhibitor; HOE-642, a Na+-H+ exchanger inhibitor; Compound RU-1355, a Na+-H+ exchanger inhibitor; RB-222, anti-VEGF neutralizing antibody; SEA0400, a specific inhibitor of the Na+-Ca2+ exchanger; BBB, blood–brain barrier; VEGF, vascular endothelial growth factor; Anti-miR-1, anti-microRNA-1; Antagomir, inhibitor of miRNA-1.
#
Note that VEGF can both promote cerebral edema and have neuroprotective effects. Aquaporin-4 has a protective effect against vasogenic edema.