Icariside II Attenuates Chronic Hydrocephalus in an Experimental Subarachnoid Hemorrhage Rat Model

Abstract

Purpose To investigate the role of ICA II in subarachnoid hemorrhage (SAH)- related chronic hydrocephalus. Methods A two hemorrhage injection model of SAH was created in Sprague Dawley rats (6-8 weeks). A total of 125 rats were randomly assigned into five groups: Sham group, SAH group, SAH+ ICA II (1 mg/kg) group, SAH + ICA II (5 mg/kg) group, and SAH + ICA II (10 mg/kg) group. TGF-β1, phospho-Smad2/3, connective tissue growth factor (CTGF), and procollagen type I carboxy-terminal propeptide (PICP) were assessed via real-time PCR, Western blotting, and enzyme-linked immunosorbent assay. Lateral ventricular index, Masson staining, and Morris water maze tests were employed to evaluate subarachnoid fibrosis, hydrocephalus, and long term neurological function following SAH. Results ICA II (1, 5, 10 mg/kg) inhibited subarachnoid fibrosis, attenuated ventriculomegaly, and effectively suppressed SAH related chronic hydrocephalus. In addition, parallel reduced expression of members of the TGF-β1/Smad/CTGF signaling pathway were observed. Importantly, ICA II may improve long term neurocognitive deficits after SAH. Conclusion ICA II might suppress fibrosis via inhibition of TGF-β1/Smad/CTGF pathway, prevent the development of SAH related chronic hydrocephalus, and improve long term neurocognitive defects following SAH.

The Pathogenesis of Hydrocephalus Following Aneurysmal Subarachnoid Hemorrhage

“…As a major downstream mediator of TGF-β1/Smad signaling in many cell types, CTGF is regarded as an important amplifier of the pro-fibrogenic action of TGF-β1 in a variety of tissues [ 56 , 57 ]. CTGF expression is also significantly increased following aSAH [ 58 , 59 ]. In experimental aSAH models, TGF-β1 concentrations in CSF and protein TGF-β1 levels are significantly increased in periventricular brain tissues [ 60 , 61 ].…”

“…Some TGF-β1 antagonists and TGF-β1 signaling pathway inhibitors alleviate chronic hydrocephalus and improve behavioral outcomes in rat aSAH models [ 58 , 59 ]. Decorin, a member of the small leucine-rich extracellular matrix proteoglycans, has exhibited significant inhibitory effects on the TGF-β1/Smad/CTGF axis, protecting against extracellular matrix accumulation with antifibrotic effects [ 59 , 63 ].…”

Risk Factor of Posthemorrhagic Hydrocephalus: Cerebrospinal Fluid Total Protein

“…CSF amyloid protein, nerve cell adhesion molecule-L1 (L1CAM), nerve cell adhesion molecule-1 (NCAM-1), and other proteins involved in nerve development are highly correlated with PHH in premature infants ( 24 ). Clinically, it is observed that there are high levels of proteins in the cerebrospinal fluid of patients with hydrocephalus, such as thrombopoietin, carbonicanhydrase-I (CA-I) and peroxidase-2 (Prx-2) ( 25 ), TGF-β1 ( 26 ), S-100protein, glial fibrillary acidic protein (GFAP) ( 27 , 28 ), neuron-specific enolase (NSE), and vascular endothelial growth factor ( 29 ). Absorption decreases after the accumulation of a large number of proteins in the ventricular system ( 30 ), leading to increased osmotic pressure and promotion of hydrocephalus ( 31 – 33 ).…”

Prediction of adult post-hemorrhagic hydrocephalus: a risk score based on clinical data

“…Currently, literature reports on hydrocephalus center on the risk factors or prediction models of a disease, whereas the pathogeneses of these diseases have common characteristics, which are gradually being recognized by the public. PHH is considered an important factor in the poor prognosis of ICH 4 , IVH 5 , SAH 6 , and TBI 7 . However, predictive models for PHH are lacking.…”