Application of taurine in treatment of hair growth matrix bleeding of premature infants

Abstract

The invention discloses an application of taurine in treatment of hair growth matrix bleeding of premature infants, and relates to a new application of taurine in preparation of a medicine for preventing or improving white matter injury after the hair growth matrix bleeding (GMH) of the premature infants. The medicine takes taurine as an active ingredient and is administered in manners of intraperitoneal injection and the like, and the preferable dosage is 120 mg / kg / day. In-vivo and in-vitro experiments show that the taurine can remarkably reverse mitochondrial dysfunction of oligodendrocyte precursor cells (OPCs) after GMH, and by activating PINK1 / Parkin mediated mitochondrial autophagy and promoting survival and maturation of the OPCs, myelin sheath formation and tissue structures are improved, and finally sensory movement and cognitive function recovery are promoted. The invention provides a strategy which is novel in mechanism and easy in clinical transformation for preventing and treating secondary white matter injury after GMH.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of application of taurine in treating germinal matrix hemorrhage (GMH) of premature infants, and in particular to the application of taurine in treating germinal matrix hemorrhage of premature infants. BACKGROUND

[0002] Germinal matrix hemorrhage (GMH) is a major neurological disease in premature infants, which seriously affects infants with gestational age less than 28 weeks or body weight less than 1500 grams, and the incidence rate is as high as 20-30%. GMH leads to white matter injury (WMI), which is characterized by loss of oligodendrocyte precursor cells (OPCs), maturation arrest, poor myelination and axonal degeneration. OPCs are the main glial cell population in white matter during 24-32 weeks of pregnancy, and their maturation depends on mitochondrial function, but mitochondrial dysfunction (such as oxidative phosphorylation damage, excessive ROS production and impaired mitochondrial autophagy) after GMH is a core factor of WMI. At present, there is no method to target OPC mitochondrial damage after GMH. Taurine is an abundant amino acid in the developing brain, which has antioxidant, mitochondrial stabilizing and anti-inflammatory effects, and has been used for parenteral nutrition in premature infants, but its application in protecting OPC mitochondrial function after GMH has not been studied.

[0003] Therefore, the present application explores taurine as a new strategy for treating GMH.

[0004] To this end, the present application proposes the application of taurine in treating germinal matrix hemorrhage of premature infants. SUMMARY

[0005] The purpose of the present application is to solve the shortcomings in the prior art, and the application of taurine in treating germinal matrix hemorrhage of premature infants.

[0006] In order to achieve the above-mentioned purpose, the present application adopts the following technical solutions: The application of taurine in treating germinal matrix hemorrhage of premature infants is used in the preparation of a drug for preventing or improving white matter injury after germinal matrix hemorrhage.

[0007] Preferably, the germinal matrix hemorrhage is germinal matrix hemorrhage of premature infants.

[0008] Preferably, the prevention or improvement of white matter injury includes any one or more of the following: promoting the survival of oligodendrocyte precursor cells, inhibiting mitochondrial dysfunction of oligodendrocyte precursor cells, promoting mitochondrial autophagy, or improving myelination.

[0009] Preferably, the promotion of mitochondrial autophagy includes regulation of the PINK1 / Parkin-dependent mitochondrial autophagy pathway.

[0010] A pharmaceutical composition for preventing or improving white matter injury after bleeding of the germinal matrix, comprising a therapeutically effective amount of taurine and a pharmaceutically acceptable carrier.

[0011] Preferably, the pharmaceutical composition is configured as a dosage form for parenteral administration.

[0012] Preferably, the parenteral administration is intraperitoneal injection.

[0013] Preferably, the therapeutically effective amount corresponds to 100-150 mg of taurine per kilogram of body weight per day.

[0014] Preferably, the therapeutically effective amount is 120 mg of taurine per kilogram of body weight per day.

[0015] Preferably, the pharmaceutical composition is configured to start administration after the occurrence of bleeding of the germinal matrix and continuous administration for at least three days.

[0016] The beneficial effects of the present application are: Novel mechanism and clear target: the prior art for the treatment of WMI after GMH focuses on resisting neuroinflammation, excitotoxicity and other secondary damage mechanisms, while the present application first discovers and confirms that the intrinsic mitochondrial dysfunction, especially the impaired mitochondrial autophagy of OPCs after GMH is the core link leading to WMI, and innovatively uses taurine to target this specific pathological process; taurine solves the problem of OPC maturation arrest from the root of energy metabolism and cell mass control by restoring PINK1 / Parkin-dependent mitochondrial autophagy, and the mechanism is clear, which is significantly different from traditional neurotrophic drugs and has technical advancement.

[0017] Strong conversion and low risk of clinical application: the active ingredient taurine used in the present application is itself a conventional component of parenteral nutrition for premature infants, and its safety for the premature infant population has been fully supported by clinical practice and data, and has small toxic and side effects; therefore, the "old drug new use" of taurine for preventing and treating WMI after GMH can greatly shorten the new drug development cycle, reduce the safety risk of preclinical and clinical research, has extremely significant advantages in translational medicine and great clinical application prospects, and is easy to quickly push to the clinic to benefit patients.

[0018] Overall effect, with short-term and long-term improvement: the present application proves through in vivo and in vitro experiments that taurine intervention not only can reduce mitochondrial damage of OPCs and promote their survival in the acute phase (within 3 days after GMH), but also can bring long-term benefits, including improving myelination, protecting white matter structural integrity, and ultimately significantly improving the long-term sensory motor and cognitive function of GMH model animals; this shows that taurine treatment can not only intervene in acute injury, but also promote neural repair and remodeling, which has great significance for improving the long-term neurodevelopmental outcome of premature infants. BRIEF DESCRIPTION OF DRAWINGS

[0019] Figure 1 and Figure 2 Figure 1 shows the schematic diagram of the result of early OPC number reduction after GMH; Figure 3 Figure 2 shows the schematic diagram of the result of taurine protecting OPC survival in vivo; Figure 4 Figure 3 shows the schematic diagram of the result of establishing thrombin-induced GMH injury model in vitro using OLN93 cell line; Figure 5 and Figure 6 Figure 4 shows the schematic diagram of the result of taurine reversing thrombin-induced OPC mitochondrial depolarization and oxidative stress; Figure 7 Figure 5 shows the schematic diagram of the result of taurine reducing OPC mitochondrial damage caused by GMH; Figure 8 Figure 6 shows the schematic diagram of the result of long-term behavioral motor performance improvement of GMH rats after taurine intervention. DETAILED DESCRIPTION

[0020] The technical solutions of the present application will be further described in detail below in combination with specific embodiments.

[0021] In the description of the present application, it should be noted that unless otherwise explicitly specified and limited, the terms “mounting”, “connecting”, “connecting”, “setting” should be understood broadly, for example, it can be fixedly connected, set, or detachably connected, set, or integrally connected, set. For those skilled in the art, the specific meaning of the above terms in the present application can be understood according to the specific circumstances.

[0022] Example 1: Experimental animal model All animal procedures were performed in accordance with institutional and national regulations governing the care and use of laboratory animals. Throughout the study, every effort was made to limit animal discomfort and only the minimum number of animals necessary to achieve reliable statistical power was used. A total of one hundred P5 Sprague-Dawley rat pups (10-14 grams, both sexes) were included in the experiment.

[0023] The GMH model used in this study has been previously described (Jinnai et al., 2020a). Briefly, P5 pups were anesthetized with isoflurane (4% induction, 2% maintenance) and placed in a stereotaxic apparatus for neonates. After the scalp was disinfected, a midline incision was made to expose the bregma, and a burr hole (1 mm) was drilled. Collagenase VII (0.3 U, C0773, Sigma-Aldrich, USA) was injected into the right basal ganglia with coordinates relative to the bregma: ant 1.8 mm, lat 1.5 mm, vent 2.8 mm. The enzyme was delivered at a rate of 1 μΐ / min using a 27-gauge needle attached to a 10-μΐ Hamilton syringe, driven by a microsyringe pump (Harvard Apparatus, Holliston, MA). After injection, the needle was left in place for 5 min to prevent backflow, and then slowly withdrawn. The bony hole was sealed with bone wax, and the incision was sutured. Pups were returned to their mothers after recovery on a 37 °C heating pad. Sham animals received the same procedure without collagenase injection. All procedures were performed in accordance with institutional animal care regulations, and the number of animals was kept to the minimum required for statistical validity, following the principles of replacement, reduction, and refinement (3Rs).

[0024] Taurine intervention protocol Taurine treatment began at the time of recovery of consciousness after GMH induction in pups (day 0 after injury). Taurine (T0625, Sigma-Aldrich, USA) was injected intraperitoneally (right lower quadrant of the abdomen) at a dose of 120 mg / kg once daily for three days (days 0-2 after injury). The solution was prepared in sterile saline and filtered through a 0.22-μιη membrane. Injection volume was adjusted according to body weight and administered within 40-60 s to minimize procedural stress. Sham and GMH control animals received an equal volume of sterile saline.

[0025] The dosing regimen was informed by early reports showing a broad neuroprotective range of taurine in rodent models (Gupte et al., 2019), as well as our own preliminary time course analysis. In the series of GMH pre-experiments (0 h, 6 h, 1 day, 3 days, 5 days, 7 days), proteins related to OPCs and mitochondrial autophagy changed most prominently around day 3, supporting a three-day treatment window.

[0026] Tissue collection and experimental time points Tissue collection was performed at predetermined acute and long-term time points. For acute analysis, brains were harvested at day 3 after injury, a time point identified by preliminary Western blotting as a key turning point for the OPC and mitochondrial response. Samples collected at this stage were used for Western blotting, immunofluorescence, transmission electron microscopy, and related assays.

[0027] For long-term assessment, the brain was collected on day 28 post-injury to evaluate the lasting effects on oligodendrocyte maturation, myelination, and white matter structure, and to correlate these effects with behavioral outcomes. For biochemical studies, the target area was rapidly dissected on ice, flash-frozen, and stored at -80°C. For histological analysis, animals were perfused with phosphate-buffered saline followed by perfusion with 4% paraformaldehyde; the brain was fixed, cryoprotected, and sectioned. All terminal procedures were performed under deep anesthesia, and tissue handling followed optimized practices designed to minimize pain.

[0028] Cell culture OLN93 cell line was purchased from the Neurosurgery Laboratory of Army Medical University. Cells were maintained in high-glucose DMEM (11965092, Gibco, China) supplemented with 10% fetal bovine serum (C04001-050X10, VivaCell, China) and 1% penicillin-streptomycin (15140148, Gibco, China). Cultures were maintained in a humidified incubator at 37°C and 5% CO2, with the medium changed every 1-2 days. At passage, cells were dissociated using 0.25% trypsin (25200056, Gibco, China). Cells from passages 5 to 20 were used for experiments to ensure phenotypic consistency.

[0029] Thrombin-induced OLN93 injury model To simulate GMH-related cell damage in vitro, OLN93 cells were exposed to thrombin (Ye et al., 2020). When the culture reached approximately 70–80% confluence, the medium was replaced with serum-free DMEM containing gradient concentrations of thrombin (T8021, Solarbio). Working solutions were prepared with serum-free DMEM at concentrations of 0, 0.1, 1, 5, 10, 20, 50, and 100 U / mL, and cell viability was assessed using CCK8 assays at 12, 24, and 48 hours. In short, OLN93 cells were seeded in 96-well plates and treated with specified thrombin concentrations. At each predetermined time point, 10 μL of CCK8 reagent (CA1210, Solarbio) was added, and the cells were incubated at 37°C in the dark for 30 minutes, followed by absorbance measurement at 450 nm. Viability curves were then used to determine the concentration-time combinations that produced a stable and reproducible damage response. Control cells received an equal volume of serum-free medium under the same conditions.

[0030] Taurine treatment in OLN93 cells Taurine was dissolved in sterile physiological saline, filtered through a 0.22-micron membrane, and freshly prepared before use. Working solutions were prepared at concentrations of 0, 1, 5, 10, 20, 50, 100, 150, and 200 mM. Cell viability was assessed using a CCK8 assay after 24 hours to determine the appropriate working concentration. After determining the optimal dose, taurine was added immediately after thrombin exposure, and incubation continued for 24 hours to assess its rescue effect. Control cultures were treated with an equal volume of serum-free DMEM under the same conditions.

[0031] Protein blot Protein extraction was performed according to a pre-established procedure (Towbin et al., 1979). Samples were placed in 1.5 mL EP tubes and lysed on ice for 30 min in RIPA lysis buffer (WB3100, NCM, China) containing PMSF (ST505, Beyotime, China). Lysates were centrifuged at 12,000 × g for 15 min at 4°C, and the supernatant was collected for SDS-PAGE. Proteins were separated on a 12.5% ​​SDS-PAGE gel and transferred to a PVDF membrane (Merck Millipore, USA). The membrane was blocked with rapid blocking buffer (PS108P, Epizyme, China) at room temperature for 30 min, then incubated overnight at 4°C with primary antibody. After washing, the membrane was incubated at room temperature for 2 h with HRP-labeled goat anti-rabbit IgG (1:40,000; Boster, Wuhan, China; catalog number #BA1055; RPID: AB_2927669). The bands were developed using ECL reagent (1:1; Zenbio, Chengdu, China; catalog number #17046) and imaged using a chemiluminescence detection system (OI600, BIO-OI, Guangzhou, China).

[0032] The primary antibodies used in this invention include: β-actin (rabbit, 1:20,000; Boster, catalog number #BA2305), NG2 (rabbit, 1:500; Invitrogen; RRID: AB_2533307), PDGFRα (rabbit, 1:1,000; Cell Signaling Technology), MBP (rabbit, 1:1,000; Cell Signaling Technology), MOG (rabbit, 1:1,000; Solarbio), PINK1 (rabbit, 1:1,000; Abmart), Parkin (rabbit, 1:1,000; Abmart), SQSTM1 / p62 (rabbit, 1:1,000; Cell Signaling Technology), LC3B (rabbit, 1:1,000; Abmart), TOMM20 (rabbit, 1:1,000; Cell Signaling Technology), and BCL-2 (rabbit, 1:1,000; Abmart). Band intensity was quantified using ImageJ software (NIH, Bethesda, USA) (Schneider et al., 2012). All experiments were performed in triplicate.

[0033] Immunofluorescence Immunofluorescence staining was performed to examine the localization and expression of PDGFRα in white matter regions. Rats were perfused with phosphate-buffered saline (PBS) via the heart, followed by perfusion with 4% paraformaldehyde. The brain was post-fixed overnight, cryoprotected in 30% sucrose, embedded, and coronally sectioned using a cryotome to a thickness of 15 μm. Sections were washed in PBS, permeated with 0.3% Triton X-100 for 15 min, and then blocked with 5% bovine serum albumin (BSA) in PBS at room temperature for 1 h. Tissue sections were then incubated overnight at 4°C with the primary antibody against PDGFRα (rabbit, 1:200; Cell Signaling Technology). After washing, sections were incubated at room temperature in the dark with a secondary antibody conjugated to an appropriate fluorescent dye (Alexa Fluor 488, 1:500) for 1 h. Cell nuclei were counterstained with DAPI (1 μg / mL), and sections were mounted with anti-fluorescence quenching mounting medium. Images were acquired using a laser scanning confocal microscope under the same acquisition settings for all groups. The density and fluorescence intensity of PDGFRα-positive cells were quantified using ImageJ software in predefined regions of interest around the ventricles and in the white matter. All analyses were performed in a blinded manner.

[0034] HE staining H&E staining was used to assess ventricular dilatation, residual hemorrhage, and other morphological changes after GMH. Paraffin-embedded brain sections (5 μm) were dewaxed in xylene I and II for 6 min each, rehydrated by gradient ethanol (100% I and II, 95%, 85%, and 75%; 6 min each), and rinsed in running tap water.

[0035] Sections were stained with hematoxylin (AFIHC007, Aifang Biotechnology) for 7 minutes, washed thoroughly, differentiated in differentiation solution (AFIHC019) for 2 seconds, and then blued in blue solution (AFIHC020) for 1 minute. After rinsing, excess surface moisture was gently removed, and sections were stained with eosin for 2 minutes. They were then dehydrated by three cycles of 100% ethanol (1 minute each), treated with n-butanol for 2 minutes, and then treated with xylene I and II for 5 minutes each to clear.

[0036] Mount the slides with neutral resin mounting medium (AFIHC043) and acquire bright-field images using a Nikon ECLIPSEE100 microscope equipped with a DS-U3 imaging system.

[0037] LFB staining Luxol fast blue (LFB) staining (Biossci, Wuhan, China) was used to assess myelin integrity and white matter damage after GMH. Paraffin-embedded brain sections (5 μm) were dewaxed in environmentally friendly clearing agents I–III for 10 min each, rehydrated by a gradient of ethanol solutions (100%, 95%, 85%, and 75%; 5 min each), and rinsed in distilled water.

[0038] The sections were then incubated in preheated LFB staining solution, either overnight at 37°C or for 2 hours at 60°C (with the container covered). After natural cooling, excess dye was removed by rinsing in distilled water. Differentiation was performed in 0.05% lithium carbonate solution until the background turned light gray, followed by further differentiation in 70% ethanol to obtain a clear gray-white contrast; the endpoint was adjusted under an optical microscope if necessary. The sections were then dehydrated by gradient ethanol, cleared with xylene, and mounted with neutral resin. Images were acquired using an Olympus CX-31 microscope equipped with a NanoZoomer imaging system. Myelinated fibers appeared blue, cell nuclei appeared dark blue, and collagen fibers appeared light pink.

[0039] Transmission electron microscope Transmission electron microscopy was performed to assess ultrastructural changes in oligodendrocytes and mitochondria. Brain tissue blocks were fixed for 24 hours at 4°C in 2.5% glutaraldehyde in 0.1 M phosphate buffer, followed by washing in the same buffer (three times, 15 minutes each). After fixation with 1% osmium tetroxide at room temperature for 2 hours, the samples were washed again with 0.1 M phosphate buffer (three times, 15 minutes each), dehydrated by a gradient of ethanol (50%, 75%, 80%, 95%, and 100%) and acetone, then infiltrated with a mixture of acetone and 812 embedding resin (2:1, 1:1, 1:2), and finally embedded in pure resin. Polymerization was performed sequentially at 37°C and 60°C.

[0040] Ultrathin sections (60–80 nm) were cut using an ultramicrotome (Leica UC7) and collected on a copper grid. Sections were stained with 2% uranyl acetate for 30 minutes and lead citrate for 15 minutes, then rinsed and air-dried. Images were acquired using a JEM-1400 transmission electron microscope (JEOL, Japan), and mitochondrial morphology, myelin tightness, and axonal integrity were assessed using a blinded method.

[0041] Behavioral tests Three behavioral tests were used to assess acute neurological function: righting reflex, negative geotropism, and suspension test. The righting reflex assessed basic motor coordination by measuring the time required for a pup to roll over to all fours after being placed in a supine position (cutoff time: 30 seconds). Each animal underwent three trials, and the average was used; puplets that failed to right themselves within the specified time were assigned the maximum delay (Merenick et al., 2024). The negative geotropism was used to assess vestibular function and early motor coordination. Puplets were placed head-down on a 20° inclined plane, and the time required to rotate 180° was recorded. Animals that failed to turn over within 120 seconds scored 0; animals that completed the task within 0-30, 31-60, 61-90, and 91-120 seconds scored 4, 3, 2, and 1, respectively (Jinnai et al., 2020b). The suspension test assessed forelimb strength and motor endurance by having puplets grasp a horizontal wire (2 mm in diameter, 25 cm above a mat), and the fall latency was recorded (cutoff time: 60 seconds). Each animal was tested three times, and the average value was used for analysis (Balkaya et al., 2013).

[0042] Long-term functional outcomes were assessed using the open field test (OFT) and longitudinal weight monitoring 28 days after GMH induction. The OFT was performed to assess spontaneous activity and anxiety-like behaviors. Rats were placed in the center of a non-reflective rectangular field (100 × 100 × 40 cm, uniformly illuminated) and allowed free exploration for 5 minutes. Behavioral parameters, including total distance traveled, proportion of large-amplitude movements, time spent in the central area, and movement trajectory, were recorded using a fully automated tracking analysis system (Video6123). The field was cleaned with 75% ethanol between tests to eliminate odor cues, and all behavioral scores and analyses were performed in a blinded manner. The experimental procedure followed the established OFT protocol (Zhang et al., 2023b). In addition, body weight was measured on days 3, 14, 21, and 28 after GMH induction to assess growth trajectory and overall physiological recovery. These time points reflect critical developmental windows and allow for assessment of delayed growth defects. Body weight data are expressed as mean ± standard deviation and compared between groups to assess long-term functional outcomes.

[0043] All tests were conducted during the daylight hours (09:00-15:00) under controlled temperatures (22-24°C) and low ambient noise.

[0044] JC-1 Mitochondrial Membrane Potential Detection Mitochondrial membrane potential (Δψm) was assessed in OLN93 cells using the JC-1 assay kit (ab113850, Abcam, UK). After the specified treatment, cells were washed twice with pre-warmed PBS and incubated for 20 min at 37°C in the dark according to the manufacturer's instructions. Following incubation, cells were gently washed with JC-1 assay buffer to remove excess dye and immediately processed for imaging or flow cytometry.

[0045] For confocal imaging, JC-1-loaded cells cultured in glass-bottom dishes were observed using a laser scanning confocal microscope. Red fluorescence of the JC-1 polymer (high Δψm) and green fluorescence of the JC-1 monomer (low Δψm) were acquired using appropriate excitation / emission settings (approximately Ex / Em 540 / 590 nm for red and approximately 485 / 530 nm for green). Mitochondrial membrane potential was quantified by calculating the red / green fluorescence intensity ratio using ImageJ; the same acquisition and analysis settings were applied to all groups.

[0046] For flow cytometry analysis, JC-1 stained cells were gently dissociated, resuspended in detection buffer, and analyzed immediately on a flow cytometer. Green (monomer JC-1) and red (polymerized JC-1) signals were collected using the FITC and PE channels, respectively. Δψm represents the ratio of red to green fluorescence, and at least 10,000 events were recorded for each sample.

[0047] FCCP, a mitochondrial uncoupling agent, was used as a positive control for mitochondrial depolarization. In the positive control group, cells were treated with FCCP (10 μM, 37°C, 20 min) before loading JC-1 to confirm the responsiveness and dynamic range of the assay.

[0048] ROS measurement Intracellular reactive oxygen species (ROS) levels were measured using a DCFH-DA-based ROS detection kit (S0033S, Beyotime, China), following the manufacturer's instructions with slight modifications. OLN93 cells were seeded in 24-well plates or glass-bottomed culture dishes and subjected to the specified treatments. At the end of the intervention, cells were washed twice with warm PBS and incubated at 37°C in the dark with DCFH-DA working solution (10 μM in serum-free medium, freshly prepared) for 30 minutes. After incubation, cells were gently washed with PBS to remove excess probe and immediately processed for imaging or flow cytometry.

[0049] For confocal imaging, laser scanning confocal microscopy was used to observe cells loaded with DCFH-DA in glass-bottom culture dishes under excitation conditions of 488 nm and emission collection conditions of 520–530 nm. ROS generation was quantified by calculating the mean fluorescence intensity (MFI) of the green signal in the region of interest using ImageJ, with the same acquisition parameters and analysis thresholds applied to all groups.

[0050] For flow cytometry, stained cells were gently dissociated, resuspended in ice-cold PBS or assay buffer, and immediately analyzed on the flow cytometer using the FITC channel. At least 10,000 events were collected per sample. ROS levels were expressed as MFI of the FITC signal and normalized to the corresponding control group.

[0051] ROSup (1:1000, Beyotime, China) was used as a positive control to validate the responsiveness and dynamic range of the test.

[0052] Statistical analysis All statistical analyses were performed using GraphPad Prism (version 10.8) and R (version 4.2.1). The normality of the data was first tested using the Shapiro–Wilk test. For normally distributed data, unpaired two-tailed Student's t-test was used for comparisons between two groups, while one-way or two-way ANOVA was used for comparisons among multiple groups, followed by Tukey's post-hoc test as appropriate. Nonparametric data were analyzed using the Mann–Whitney U test or the Kruskal–Wallis test with Dunn correction. Results are expressed as mean ± standard deviation unless otherwise stated. A p-value < 0.05 was considered statistically significant.

[0053] Pearson correlation analysis was performed to examine the association between mitochondrial / OPC markers and functional outcomes. Correlation strength and significance were reported using Pearson's r and corresponding p-values.

[0054] All analyses were performed in a blinded manner, and each experiment consisted of at least three independent biological replicates.

[0055] The above description is only a preferred embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any equivalent substitutions or modifications made by those skilled in the art within the scope of the technology disclosed in the present invention, based on the technical solution and inventive concept of the present invention, should be covered within the scope of protection of the present invention.

Claims

1. The application of taurine in the treatment of germinal matrix hemorrhage in premature infants, characterized in that, It is used in the preparation of drugs for preventing or improving white matter damage after bleeding of the hair follicle matrix.

2. The application of taurine according to claim 1 in the treatment of germinal matrix hemorrhage in preterm infants, characterized in that, The hemorrhage in the hair follicle refers to hemorrhage in the hair follicle of premature infants.

3. The application of taurine according to claim 1 in the treatment of germinal matrix hemorrhage in preterm infants, characterized in that, The prevention or improvement of white matter damage includes any one or more of the following: promoting oligodendrocyte precursor cell survival, inhibiting oligodendrocyte precursor cell mitochondrial dysfunction, promoting mitophagy, or improving myelin formation.

4. The application of taurine according to claim 3 in the treatment of germinal matrix hemorrhage in preterm infants, characterized in that, The promotion of mitophagy includes regulating the PINK1 / Parkin-dependent mitophagy pathway.

5. A pharmaceutical composition for preventing or improving white matter damage following bleeding of the dermal matrix, characterized in that, It contains a therapeutically effective amount of taurine and a pharmaceutically acceptable carrier.

6. The pharmaceutical composition according to claim 5 for preventing or improving white matter damage following dermal matrix hemorrhage, characterized in that, The pharmaceutical composition is formulated as a dosage form for parenteral administration.

7. The pharmaceutical composition according to claim 6 for preventing or improving white matter damage following dermal matrix hemorrhage, characterized in that, The parenteral administration is administered via intraperitoneal injection.

8. The pharmaceutical composition according to claim 5 for preventing or improving white matter damage following bleeding of the dermal matrix, characterized in that, The therapeutically effective dose corresponds to 100 to 150 mg of taurine per kilogram of body weight per day.

9. The pharmaceutical composition according to claim 8 for preventing or improving white matter damage following follicular matrix hemorrhage, characterized in that, The effective therapeutic dose is 120 mg of taurine per kilogram of body weight per day.

10. The pharmaceutical composition according to claim 5 for preventing or improving white matter damage following dermal matrix hemorrhage, characterized in that, The pharmaceutical composition is configured to be administered after the occurrence of bleeding in the hair follicle matrix and continuously for at least three days.

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