Decreased MiR-30a promotes TGF-β1-mediated arachnoid fibrosis in post-hemorrhagic hydrocephalus

Abstract

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Fibrosis in the ventricular system is closely associated with post-hemorrhagic hydrocephalus (PHH). It is characterized by an expansion of the cerebral ventricles due to CSF accumulation following intraventricular hemorrhage (IVH). The activation of transforming growth factor-β1 (TGF-β1) may be involved in thrombin-induced arachnoid fibrosis.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>A rat model of PHH was established by injection of autologous non-anticoagulated blood from the right femoral artery into the lateral ventricles. Differential expression of miR-30a was detected in rat arachnoid cells by RNA sequencing. AP-1, c-Fos, and TRAF3IP2 were knocked down in primary arachnoid cells, and the degree of arachnoid fibrosis was assessed.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Decreased expression of miR-30a and increased expression of TRAF3IP2, TGF-β1, and α-SMA were detected in the arachnoid cells of PHH rat. Besides, overexpression of miR-30a targets TRAF3IP2 mRNA 3′UTR and inhibits the expression of TRAF3IP2, TGF-β1, and α-SMA in the primary arachnoid cells. Furthermore, TRAF3IP2 activates AP-1 to promote arachnoid fibrosis. The content of type I collagen in the primary arachnoid cells was reduced after the silencing of AP-1 and TRAF3IP2.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>This study identified a miR-30a-regulated mechanism of arachnoid fibrosis, suggesting a previously unrecognized contribution of miR-30a to the pathogenesis of fibrosis in the ventricular system. These results might provide a new target for the clinical diagnosis and treatment of PHH.</jats:p></jats:sec>

Novel therapeutics for hydrocephalus: Insights from animal models

“…Researchers tried to interfere with the TGF‐β pathway as a means to treat hydrocephalus in animal models 59,60 . Manaenko et al administered SD208, a TGF receptor I inhibitor, daily for 3 days after GMH induction and compared the result with vehicle‐treated GMH rats.…”

“…Researchers tried to interfere with the TGF‐β pathway as a means to treat hydrocephalus in animal models. 59 , 60 Manaenko et al administered SD208, a TGF receptor I inhibitor, daily for 3 days after GMH induction and compared the result with vehicle‐treated GMH rats. The results showed that high‐dose SD208 inhibited GMH‐induced activation of the TGF‐β pathway, reduced the deposition of vitronectin, and alleviated brain atrophy and hydrocephalus.…”

Ependymal Cilia: Physiology and Role in Hydrocephalus

“…Because NPH is frequently detected in people with Alzheimer’s disease, the current hypothesis proposes that NPH is the outcome of neurodegenerative alterations in AD patients. The removal of toxic molecules such as Aβ is aided by the circulation of CSF ( Zhan et al, 2020 ).…”

Surgical Treatment for Pediatric Hydrocephalus: a Report of 163 Clinical Cases in a Single Center

“…Preoperative MRI cerebrospinal uid ow imaging will be added to patients in our department to observe whether the base of the third ventricle is bulging downward or sagging and whether the ow of cerebrospinal uid in the mesencephalic aqueduct is unobstructed to aid in differentiation [29]. For patients with typical symptoms of normal pressure hydrocephalus, our department performs a preoperative cerebrospinal uid tap test to assess the prognosis of the patient, whose speci c operation is to administer a single dose of 40-60ml of cerebrospinal uid at a single time and observe the improvement of the patient's symptoms 24-48 hours after the uid release [33]. According to the Japanese Neurosurgical Association's guidelines for the management of idiopathic normal pressure hydrocephalus (NPH) [16] and the American Idiopathic NPH Study Group's guidelines [20], the positive predictive value of the uid release test is 73%-100%.…”