Alterations of caveolin-1 expression in a mouse model of delayed cerebral vasospasm following subarachnoid hemorrhage

Abstract

The aim of the present study was to evaluate the expression levels of caveolin-1 in the basilar artery following delayed cerebral vasospasm (DCVS) in a rat model of subarachnoid hemorrhage (SAH), in order to investigate the association between caveolin-1 and DCVS, and its potential as a treatment for DCVS of SAH. A total of 150 Sprague Dawley rats were randomly allocated into blank, saline and SAH groups. The SAH and saline groups were subdivided into days 3, 5, 7 and 14 following the establishment of the model. The murine model of SAH was established by double injection of autologous arterial blood into the cisterna magana and DCVS was detected using Bederson neurological severity scores. Hematoxylin and eosin (HE) staining was used to observe the inner perimeter of the basilar artery pipe and variations in the thickness of the basilar artery wall. Alterations in the levels of caveolin-1 protein in the basilar artery were measured using immunofluorescence and western blot analysis; whereas alterations in the mRNA expression levels of caveolin-1 were detected by reverse transcription-quantitative polymerase chain reaction. In the present study, 15 mice succumbed to SAH-induced DCVS in the day 3 (n=3), 5 (n=5) and 7 (n=2) groups. No mortality was observed in the blank control and saline groups during the process of observation in the SAH group, All mice in the SAH groups exhibited Bederson neurological severity scores ≥1; whereas no neurological impairment was detected in the blank and normal saline groups, demonstrating the success of the model. HE staining was used to assess vasospasm and the results demonstrated that the inner perimeter of the basal artery pipe decreased at day 3 in the SAH group; whereas values peaked in the day 7 group. The thickness of the basal artery wall significantly increased (P<0.05), as compared with the blank and saline groups, in which no significant alterations in the wall thickness and the inner perimeter of the basal artery pipe were detected. As detected by immunofluorescence and western blot analysis, the expression levels of caveolin-1 protein significantly decreased in the day 7 of SAH group, as compared with the blank and saline groups (P<0.01), in which no significant alterations were detected. Caveolin-1 mRNA expression levels significantly increased at the day 7 in the SAH group, as compared with the blank and the saline groups (P<0.01), as detected by RT-qPCR. Furthermore, significant differences were detected at day 14 in the SAH group, as compared with the blank and the saline groups (P>0.05), in which no significant alterations were detected. Therefore, the results of the present study demonstrated that caveolin-1 protein was downregulated in the basilar artery of a rat modeling SAH, which may be associated with DCVS. This suggested that caveolin-1 may be a potential target for the treatment of DCVS.

Potential role of poly (ADP‑ribose) polymerase in delayed cerebral vasospasm following subarachnoid hemorrhage in rats

“…According to clinical presentation and experimental data (15,17,18), cerebral vasospasm (CVS) can be divided into two types, acute CVS and DCVS. Acute CVS arises immediately following SAH and recovers within several hours.…”

“…Neurobehavioral tests and HE staining were performed to assess the different aspects of DCVS degree in the formal study. Generally, the DCVS is detected by the neurobehavioral score and HE staining (the artery wall thickness and internal diameter) (8,9,15). The neurobehavioral score is less specific because the neurobehavioral impairment could occur in a number of brain injuries, including cerebral ischemia and rehaemorrhagia.…”

“…The isolated basilar artery was embedded by tissue embedding station (KD-BMII; Kedee Pathology Instruments, Co., Ltd., Zhejiang, China) and made into paraffin sections by microtome (RM2235; Leica Microsystems GmbH, Wetzlar, Germany). According to a previous study (15), brainstems were fixed with 10% formalin for 24 h at 4°C and the paraffin-embedded basilar artery sections (4-µm in thickness) were deparaffinized, hydrated, washed, and stained with hematoxylin and eosin at room temperature for 10 and 5 min, respectively. By observing the pathology of basilar artery under a light microscope (BX40; Olympus Corporation, Tokyo, Japan), the wall thickness and internal diameter were calculated using an image analysis system (Q550CW; Leica Microsystems GmbH).…”

Chemical characterization and effects of volatile oil of Alpinia zerumbet on the quality of collagen deposition and caveolin-1 expression in a muscular fibrosis murine model

“…After the RT reaction, CAV-1 gene expression was performed through quantitative reverse transcription polymerase chain reaction (RT-qPCR) using the Power SYBR Green Master Mix kit (ThermoFisher Scientific), following the manufacturer's guidelines. Caveolin-1 F (5'-GACCCCAAGCATCTCAACGA-3') and Caveolin-1 R (5'-GCCATAGGGATGCCGAAGA-3') primers were used (Xiong et al, 2016). β-MG gene expression provided a reference and was measured using F (5'-TGTCTCAGTTCCACCCACCT-3') and R (5'-GGGCTCCTTCAGAGTGACG-3') primers (Krasteva et al, 2006).…”

Intracranial Pressure Measurement of and Investigation of the Effect of Aquaporin on Hydrocephalus Induced byExperimental Kaolin and Autologous Blood Injection: An Animal Study

“…2 In one subarachnoid hemorrhage (SAH) model, the autologous arterial blood of the animal is injected into the cisterna magna with the help of a needle in the prone position. 3 Hydrocephalus exacerbates neurological deficits after SAH and manifests in various neurological conditions ranging from simple cognitive dysfunction to severe gait disturbance. SAH is a common cause of chronic communicating hydrocephalus encountered in the clinic and yields clinical findings associated with hydrocephalus in 20% of patients.…”