New drugs on the horizon for cerebral edema: what’s in the clinical development pipeline?

References

• Stokum JA, Gerzanich V, Sheth KN, et al. Emerging pharmacological treatments for cerebral edema: evidence from clinical studies. Annu Rev Pharmacol Toxicol. 2020;60:291–309.
   PubMed Web of Science ®Google Scholar
• Kochanek KD, Xu J, Murphy SL, et al. Deaths: final data for 2009. Nat Vital Stat Rep. 2011;60:1–116.
   PubMedGoogle Scholar
• Mokri B. The monro-kellie hypothesis: applications in CSF volume depletion. Neurology. 2001;56:1746–1748.
   PubMed Web of Science ®Google Scholar
• King ZA, Sheth KN, Kimberly WT, et al. Profile of intravenous glyburide for the prevention of cerebral edema following large hemispheric infarction: evidence to date. Drug Des Devel Ther. 2018;12:2539–2552.
   PubMed Web of Science ®Google Scholar
• Shah S, Kimberly WT. Today’s approach to treating brain swelling in the neuro intensive care unit. Semin Neurol. 2016;36:502–507.
   PubMed Web of Science ®Google Scholar
• Stokum JA, Gerzanich V, Simard JM. Molecular pathophysiology of cerebral edema. J Cereb Blood Flow Metab. 2016;36:513–538.
   PubMed Web of Science ®Google Scholar
• Koenig MA. Cerebral edema and elevated intracranial pressure. Continuum. 2018;24:1588–1602.
   PubMedGoogle Scholar
• Huang H, Song S, Banerjee S, et al. The WNK-SPAK/OSR1 kinases and the cation-chloride cotransporters as therapeutic targets for neurological diseases. Aging Dis. 2019;10:626.
   PubMed Web of Science ®Google Scholar
• Zhang J, Bhuiyan MI, Zhang T, et al. Modulation of brain cation-Cl− cotransport via the SPAK kinase inhibitor ZT-1a. Nat Commun. 2020;11:78.
   PubMed Web of Science ®Google Scholar
• Mehta RI, Tosun C, Ivanova S, et al. Sur1-Trpm4 cation channel expression in human cerebral infarcts. J Neuropathol Exp Neurol. 2015;74:835–849.
   PubMed Web of Science ®Google Scholar
• Mehta RI, Ivanova S, Tosun C, et al. Sulfonylurea receptor 1 expression in human cerebral infarcts. J Neuropathol Exp Neurol. 2013;72:871–883.
   PubMed Web of Science ®Google Scholar
• Simard JM, Chen M, Tarasov KV, et al. Newly expressed SUR1-regulated NCCa-ATP channel mediates cerebral edema after ischemic stroke. Nat Med. 2006;12:433–440.
   PubMed Web of Science ®Google Scholar
• Simard JM, Tsymbalyuk N, Tsymbalyuk O, et al. Glibenclamide is superior to decompressive craniectomy in a rat model of malignant stroke. Stroke. 2010;41:531–537.
   PubMed Web of Science ®Google Scholar
• Kurland DB, Gerzanich V, Karimy JK, et al. The Sur1-Trpm4 channel regulates NOS2 transcription in TLR4-activated microglia. J Neuroinflammation. 2016;13:130.
   PubMed Web of Science ®Google Scholar
• Loh KP, Ng G, Yu CY, et al. TRPM4 inhibition promotes angiogenesis after ischemic stroke. Pflügers Arch - Eur J Physiol. 2014;466:563–576.
   PubMed Web of Science ®Google Scholar
• Jain RK. Tumor angiogenesis and accessibility: role of vascular endothelial growth factor. Semin Oncol. 2002;29:asonc02906q0003.
   Web of Science ®Google Scholar
• Dvorak HF. Vascular permeability factor/vascular endothelial growth factor: a critical cytokine in tumor angiogenesis and a potential target for diagnosis and therapy. J Clin Oncol. 2002;20:4368–4380.
   PubMed Web of Science ®Google Scholar
• Folkins C, Man S, Xu P, et al. Anticancer therapies combining antiangiogenic and tumor cell cytotoxic effects reduce the tumor stem-like cell fraction in glioma xenograft tumors. Cancer Res. 2007;67:3560–3564.
   PubMed Web of Science ®Google Scholar
• Gerstner ER, Duda DG, Di Tomaso E, et al. VEGF inhibitors in the treatment of cerebral edema in patients with brain cancer. Nat Rev Clin Oncol. 2009;6:229–236.
   PubMed Web of Science ®Google Scholar
• Chinot OL, Wick W, Mason W, et al. Bevacizumab plus radiotherapy–temozolomide for newly diagnosed glioblastoma. N Engl J Med. 2014;370:709–722.
   PubMed Web of Science ®Google Scholar
• Batchelor TT, Sorensen AG, Di Tomaso E, et al. AZD2171, a pan-VEGF receptor tyrosine kinase inhibitor, normalizes tumor vasculature and alleviates edema in glioblastoma patients. Cancer Cell. 2007;11:83–95.
   PubMed Web of Science ®Google Scholar
• Kamoun WS, Ley CD, Farrar CT, et al. Edema control by cediranib, a vascular endothelial growth factor receptor–targeted kinase inhibitor, prolongs survival despite persistent brain tumor growth in mice. J Clin Oncol. 2009;27:2542–2552.
   PubMed Web of Science ®Google Scholar
• Reeson P, Tennant KA, Gerrow K, et al. Delayed inhibition of VEGF signaling after stroke attenuates blood-brain barrier breakdown and improves functional recovery in a comorbidity-dependent manner. J Neurosci. 2015;35:5128–5143.
   PubMed Web of Science ®Google Scholar
• Greenberg DA, Jin K. Vascular endothelial growth factors (VEGFs) and stroke. Cell Mol Life Sci. 2013;70:1753–1761.
   PubMed Web of Science ®Google Scholar
• Abrams DA, Hanson JA, Brown JM, et al. Timing of surgery and bevacizumab therapy in neurosurgical patients with recurrent high grade glioma. J Clin Neurosci. 2015;22:35–39.
   PubMed Web of Science ®Google Scholar
• Barreca T, Gandolfo C, Corsini G, et al. Evaluation of the secretory pattern of plasma arginine vasopressin in stroke patients. Cerebrovasc Dis. 2001;11:113–118.
   PubMed Web of Science ®Google Scholar
• Cui H, He G, Yang S, et al. Inappropriate antidiuretic hormone secretion and cerebral salt-wasting syndromes in neurological patients. Front Neurosci. 2019;13. DOI:10.3389/fnins.2019.01170
   Web of Science ®Google Scholar
• Can B, Oz S, Sahinturk V, et al. Effects of conivaptan versus mannitol on post-ischemic brain injury and edema. Eur J Med. 2019;51:42–48.
   Web of Science ®Google Scholar
• Ghali J. Conivaptan and its role in the treatment of hyponatremia. Drug Des Devel Ther. 2009;253. DOI:10.2147/DDDT.S4505.
   Google Scholar
• Chen C. COX-2’s new role in inflammation. Nat Chem Biol. 2010;6:401–402.
   PubMed Web of Science ®Google Scholar
• Chu K, Jeong S-W, Jung K-H, et al. Celecoxib induces functional recovery after intracerebral hemorrhage with reduction of brain edema and perihematomal cell death. J Cereb Blood Flow Metab. 2004;24:926–933.
   PubMed Web of Science ®Google Scholar
• Park H-K, Lee S-H, Chu K, et al. Effects of celecoxib on volumes of hematoma and edema in patients with primary intracerebral hemorrhage. J Neurol Sci. 2009;279:43–46.
   PubMed Web of Science ®Google Scholar
• Lee S-H, Park H-K, Ryu W-S, et al. Effects of celecoxib on hematoma and edema volumes in primary intracerebral hemorrhage: a multicenter randomized controlled trial. Eur J Neurol. 2013;20:1161–1169.
   PubMed Web of Science ®Google Scholar
• Hannun YA, Obeid LM. Principles of bioactive lipid signalling: lessons from sphingolipids. Nat Rev Mol Cell Biol. 2008;9:139–150.
   PubMed Web of Science ®Google Scholar
• Salas-Perdomo A, Miró-Mur F, Gallizioli M, et al. Role of the S1P pathway and inhibition by fingolimod in preventing hemorrhagic transformation after stroke. Sci Rep. 2019;9:8309.
   PubMed Web of Science ®Google Scholar
• Sanchez T, Skoura A, Wu MT, et al. Induction of vascular permeability by the sphingosine-1-phosphate receptor–2 (S1P2R) and its downstream effectors ROCK and PTEN. Arterioscler Thromb Vasc Biol. 2007;27:1312–1318.
   PubMed Web of Science ®Google Scholar
• Wei Y, Yemisci M, Kim -H-H, et al. Fingolimod provides long-term protection in rodent models of cerebral ischemia. Ann Neurol. 2011;69:119–129.
   PubMed Web of Science ®Google Scholar
• Sehr T, Akgün K, Haase R, et al. Fingolimod Leads to immediate immunological changes within 6 h after first administration. Front Neurol. 2020;11. DOI:10.3389/fneur.2020.00391
   PubMed Web of Science ®Google Scholar
• Takahashi K. Effect of dosage reduction on peripheral blood lymphocyte count in patients with multiple sclerosis receiving long-term fingolimod therapy. J Clin Neurosci. 2019;63:91–94.
   PubMed Web of Science ®Google Scholar
• Murayi R, Chittiboina P. Glucocorticoids in the management of peritumoral brain edema: a review of molecular mechanisms. Child Nerv Syst. 2016;32:2293–2302.
   PubMed Web of Science ®Google Scholar
• Tjuvajev J, Uehara H, Desai R, et al. Corticotropin-releasing factor decreases vasogenic brain edema. Cancer Res. 1996;56:1352–1360.
   PubMed Web of Science ®Google Scholar
• Villalona-Calero MA, Eckardt J, Burris H, et al. A phase I trial of human corticotropin-releasing factor (hCRF) in patients with peritumoral brain edema. Ann Oncol. 1998;9:71–77.
   PubMed Web of Science ®Google Scholar
• Recht L, Mechtler LL, Wong ET, et al. Steroid-sparing effect of corticorelin acetate in peritumoral cerebral edema is associated with improvement in steroid-induced myopathy. J Clin Oncol. 2013;31:1182–1187.
   PubMed Web of Science ®Google Scholar
• Kitchen P, Salman MM, Halsey AM, et al. Targeting aquaporin-4 subcellular localization to treat central nervous system edema. Cell. 2020;181:784–799.e19.
   PubMed Web of Science ®Google Scholar
• Arvold ND, Armstrong TS, Warren KE, et al. Corticosteroid use endpoints in neuro-oncology: response assessment in neuro. Oncol working group. Neuro Oncol. 2018;20:897–906.
   PubMed Web of Science ®Google Scholar