Therapeutic Potential of Melatonin, Erythropoietin, and TRPV4 Antagonism in a Preclinical Model of Genetic Hydrocephalus

Triple therapy with erythropoietin, melatonin, and the TRPV4 antagonist RN1734 prevents further ventriculomegaly progression in Tmem67-- rats from P7 to P14.

• Why it matters: Surgical CSF diversion is invasive and can fail, and congenital hydrocephalus from genetic causes needs non-surgical strategies targeting ventricular pathology and downstream inflammation.
• What they did: In a Tmem67-- rat model, MRI tracked ventriculomegaly from P7 to P15, while protein analyses assessed periventricular TLR4 and NLRP3-associated inflammatory signaling after EPO+MLT, RN1734, or triple therapy.
• The result: Triple therapy reduced periventricular TLR4 and NLRP3 protein abundance and ameliorated periventricular white matter and ependymal lining structural alterations linked to hydrocephalus.

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