This study is a prospective, interventional and double-blind randomized controlled clinical trial. After approval of the clinical registry, patients who meet the standards of inclusion and exclusion criteria will be recruited to this study, if they and their relatives are willing to join the study. According to the clinical manifestations of the patients at admission and the results of cranial imaging, the patients' conditions were evaluated using the modified Fisher score, the World Federation of Neurological Surgeons Scale (WFNSS), the max-ICH score (max-ICH), the IVH score (IVHs), the Hijdra Sum Score (Hijdra), the Modified Graeb Score (mGS) and other grading criteria. Two groups (NS group and MACSF group) were divided into groups using a completely stratified randomization method. This study was a double-blind clinical study, and the grouping protocol was managed by the project research assistant. After the subject or his/her family members sign the informed consent, the project research assistant completed the grouping according to the randomly assigned sequence given by the clinical research center of the First Affiliated Hospital of Xi'an Jiaotong University. The project research assistant records the group and informs the specialist of the type of replacement fluid required. The replacement fluid was sent into the ward in a special container, and then lumbar puncture and CSF replacement were performed by the operator. The replacement liquid used in both groups was identical in appearance, color, temperature, and smell. During the whole study, the investigator did not participate in the preparation of the replacement liquid, and the subjects and their family members were also unaware of the grouping. After the case collection and electronic database records are completed, the research assistant will inform the researcher of the group name under the supervision of the third party to complete the unblinding, and the researcher shall inform the subjects of the group name in written form. For the control group, patients have treated the normal saline (0.9% Sodium Chloride Injection) as the replacement fluid. For the intervention group, MACSF will be used. The composition and concentration of MACSF is as follows:Na+: 146.2 mEq/L, K+: 2.7 mEq/L, Mg2+: 4.2 mEq/L, Cl-: 123 mEq/L, HCO3-:23.2 mEq/L, Glucose: 0.75 g/L. MACSF is prepared by the Pharmacy Intravenous Admixture Services staff of First Affiliated Hospital of Xi'an Jiaotong University, according to a specific formula in the specific working area. The whole procedure follows the aseptic principles strictly. Fresh-made MACSF will be placed in a specific container and sent to the patient ward through specific channels. Intracranial pressure (ICP) was measured by a non-invasive ICP test before lumbar puncture. If it is higher than 350cmH2O, a lumbar puncture can be performed 30 minutes after an intravenous drip of 100ml 20% mannitol. Then, for the patients who signed the informed consent, a CSF sample (3ml) was taken before each lumbar puncture CSF replacement and synchronous blood samples (6ml) were taken. The blood samples should be drawn into a non-anticoagulant tube and a heparin anticoagulant tube respectively. All the samples will be transferred to BioBank of the First Affiliated Hospital of Xi'an Jiaotong University in a liquid nitrogen tank. After re-melted in a water bath of 37°, the blood samples will be centrifuged at 4° for 15min at 3000r/min, the CSF samples will be centrifuged at 4° for 10min at 1000r/min and then the supernatant will be collected and stored at -80°. At the end of this study, the contents of oxyhemoglobin (oxy-Hb), S100 calcium-binding protein β (S100β), neuron-specific enolase(NSE), D-dimer (DD), matrix metalloproteinases-9 (MMP-9), Mg2+, Ca2+ in the samples will be detected by enzyme-linked immunosorbent assay (ELISA) or mass spectrometry. The total amount of replacement was generally 30ml, and the replacement was performed once every 2 days. When the red cell (RBC) count in CSF is less than 100×10\^6/L, the CSF is considered to be cleared. CSF replacement is performed up to four times. NIHSS and GCS scores were evaluated daily after admission. Cerebral computerized tomography (CT) was performed at least every week after admission. If there are new low-density lesions, delayed cerebral infarction (DCI) will be diagnosed. A transcranial Doppler(TCD) examination was performed the first three days after admission and after each replacement. Cerebral autoregulation (CA) was evaluated by transient hyperemic response test (THRT), a transcranial Doppler (TCD)-based CA evaluation method, which describes the changes in cerebral blood fow velocity after a brief compression of the ipsilateral common carotid artery. The specific content is described later. CVS will be diagnosed by TCD, the diagnostic criteria will be described later. All subjects were followed up on the 14, 30, 60, and 90 days after onset, and the mRS was evaluated. Meanwhile, some indicators will be used to evaluate the safety of MACSF application, which include secondary infection, fluctuation of intracranial pressure, and hypermagnesemia. For patients or their family members who do not agree to do the CSF replacement, the sample collection can be used as a supplementary analysis for this study after they sign the informed consent for sample collection.

The diagnostic criteria and the solutions will be described in the next part.