Application of chest protection in improvement of impact brain injury cognitive function influence

Abstract

The invention discloses application of chest protection in improving impact brain injury cognitive function influence, and relates to the technical field of biomedical engineering. Comprises: a rigid protective housing having a shape adapted to cover a main area of a torso of a subject; the energy dissipation inner core is borne by the rigid protective shell, is made of a polyurea polymer and is used for absorbing and dissipating impact energy through material deformation and stress dispersion when being subjected to impact wave load; and the fixing part is connected with the rigid protective shell and is used for stably fixing the chest protective device on the trunk of the object and exposing the head outside. The limitation of traditional brain injury protection is broken through, and experiments prove that under the plateau impact injury condition, non-direct injury target organs (lungs) are efficiently protected, and secondary brain injury and cognitive impairment can be remarkably relieved; the invention discloses a lung-brain interaction mechanism, and provides a brand new thought and target spot for impact injury protection.

Description

Technical Field

[0001] This invention relates to the field of biomedical engineering technology, and in particular to the application of chest protection in improving the cognitive function impact of shock-induced brain injury. Background Technology

[0002] The main characteristics of the high-altitude environment are low pressure and low oxygen (hypobaric hypoxia, HH). The brain, as the organ most sensitive to hypoxia, suffers cognitive impairment after acute hypoxia exposure. Modern warfare uses a large number of high-energy, high-explosive weapons, causing primary blast injuries via shock waves propagating through the cranium and secondary blast injuries caused by fragments or shrapnel. While helmets have historically provided good protection against fragments, the complex anatomical structure of the brain and its limited fit to helmets are insufficient to address the pervasive propagation characteristics of blast shock waves. In fact, the lungs, as the primary air-containing organ and a target organ for blast injury, withstand lower peak shock wave pressures than head injuries under 50% survival conditions, and have complex functional connections with the brain under physiological and pathological conditions. To date, the mechanisms of cognitive function and secondary brain injury following acute high-altitude hypoxia exposure are unknown; strengthening chest protection may be a potential measure to improve secondary brain injury.

[0003] Synaptic plasticity is the neural basis of learning and memory in the brain. The BDNF / TrkB signaling pathway is a key pathway for neuronal growth, development, and synaptic plasticity. Brain-derived neurotrophic factor (BDNF) specifically binds to the TrkB receptor, leading to TrkB phosphorylation, activation of downstream PI3K, phosphorylation and activation of AKT, upregulation of its downstream substrate mTOR phosphorylation, and promotion of the expression of synaptic proteins synaptophysin (SYN) and postsynaptic density protein 95 (PSD95), thereby improving learning and memory abilities. Significant changes in cognitive function follow high-altitude shock injuries, with hippocampal neuronal synaptic function and BDNF-PI3K-AKT-mediated synaptic plasticity alterations potentially playing a crucial role in cognitive impairment.

[0004] Therefore, this study employed an acute high-altitude hypoxia-induced brain injury model to investigate the mechanism of action of high-altitude brain injury by examining changes in hippocampal plasticity and the protective effect of effective chest protection against secondary brain injury caused by high-altitude brain injury. The aim was to reveal the role of the "lung-brain interaction" effect in the impairment of central nervous system function caused by lung injury, explore the impact of chest protection on brain injury, and provide new strategies for the prevention and treatment of secondary brain injury following high-altitude brain injury. Summary of the Invention

[0005] The purpose of this invention is to address the shortcomings of existing technologies by proposing the application of chest protection in improving cognitive function in patients with traumatic brain injury.

[0006] To achieve the above objectives, the present invention adopts the following technical solution: A chest protection device for mitigating cognitive impairment caused by traumatic brain injury, comprising: A rigid protective shell, the shape of which is adapted to cover the main area of ​​the object's torso; The energy dissipation core, supported by the rigid protective shell, is made of polyurea polymer and is used to absorb and dissipate impact energy through material deformation and stress dispersion when subjected to shock wave load. A fixing component, connected to the rigid protective shell, is used to stably fix the chest protection device to the object's torso and expose the head.

[0007] Preferably, the main region is the chest and abdomen.

[0008] Preferably, the rigid protective shell is composed of inner and outer nested steel sleeves, and the polyurea polymer is poured and filled into the annular space between the inner and outer sleeves, forming a composite structure after curing.

[0009] Preferably, the protective device is configured to reduce lung injury caused by shock waves after exposure to a low-pressure, low-oxygen environment, thereby indirectly improving secondary brain injury and the resulting cognitive deficits.

[0010] A method for manufacturing a chest protection device as described above includes the following steps: A mold is provided, the mold having a cavity adapted to the contour of the torso; The polyurea polymer precursor mixture is poured into the mold; Under controlled temperature and ventilation conditions, the polymer is cured and molded to form an energy-dissipating inner core; The cured inner core is integrated and assembled with the rigid protective shell, and fixing components are installed.

[0011] A method for applying chest protection to improve cognitive function in traumatic brain injury includes the following steps: Pretreatment steps: Expose the subjects to low-pressure and low-oxygen conditions simulating a high-altitude environment for a set period of time; Impact application step: Immediately after the pretreatment step, a shock wave load with set parameters is applied to the test object; Protective measures: At least simultaneously with the impact application step, the subject is fitted with a chest protection device as described above to protect their chest and abdomen from direct impact injury.

[0012] Preferably, in the pretreatment step, the altitude of the low-pressure, low-oxygen conditions simulated is 3000-5000 meters, and the exposure time is 12-48 hours; in the impact application step, the peak overpressure of the shock wave is 300-500 kPa.

[0013] A composition for treating or preventing secondary cognitive impairment following traumatic brain injury, the composition comprising an agent capable of enhancing the activity of the brain-derived neurotrophic factor signaling pathway, and the composition being designed for use in conjunction with the aforementioned method of applying chest protection to improve cognitive function following traumatic brain injury, to synergistically promote the expression of hippocampal synaptic plasticity-related proteins.

[0014] Preferably, the brain-derived neurotrophic factor signaling pathway is the BDNF / TrkB-PI3K-AKT-mTOR pathway, and the synaptic plasticity-related proteins include PSD95 and SYN1.

[0015] A method for constructing an animal model to evaluate the protective effect of chest protection on cognitive function in patients with traumatic brain injury, comprising: Animal selection: Healthy adult male C57BL / 6 mice were selected; High-altitude exposure modeling: Mice were placed in a hypobaric chamber to simulate an altitude environment of 4000 meters for 24 hours to establish an acute high-altitude exposure model; Impact injury modeling: Immediately after the high-altitude exposure, the mice were fixed in the standard right lateral decubitus position, and a shock wave with a driving pressure of 4.0 MPa was applied using a bio-shock tube to establish a trunk impact injury model. Protective intervention group setup: Before the impact, mice in the experimental group were fitted with the chest protection device as described in any one of claims 1-3, while mice in the model group were not fitted with it, in order to construct an animal model of protective intervention for comparative evaluation.

[0016] The beneficial effects of this invention are as follows: 1. This invention breaks through the limitations of traditional brain injury protection. Through experiments, it has been demonstrated that under the conditions of high-altitude impact injury, highly effective protection of the non-directly damaged target organ (lung) can significantly reduce secondary brain injury and cognitive dysfunction. This reveals a lung-brain interaction mechanism and provides a new approach and target for impact injury protection.

[0017] 2. The chest protection device and application method provided by the present invention can comprehensively reduce the damage caused by high-altitude impact injuries from the physiological and behavioral levels; specifically, it significantly improves lung function and restores normal exploratory behavior and anxiety levels, which is directly related to the protection of higher cognitive functions such as learning and memory.

[0018] 3. The protective device used in this invention can effectively disperse and dissipate shock wave energy through a composite structure of a rigid shell and polyurea-based energy-absorbing material; its manufacturing process is simple, the cost is controllable, and it has good stability and repeatability. Attached Figure Description

[0019] Figure 1 This is a graph showing the lung function analysis of mice after injury according to the present invention; Figure 2 This is an analysis diagram of the elevated cruciate maze in mice after injury, as presented in this invention. Figure 3 This is a schematic diagram illustrating the expression of mouse hippocampal synaptic plasticity-related proteins according to the present invention; Figure 4 This is a schematic diagram illustrating the expression of mouse hippocampal synaptic plasticity-related proteins according to the present invention. Detailed Implementation

[0020] The technical solution of the present invention will be further described in detail below with reference to specific embodiments.

[0021] Example 1: Application of chest protection in improving cognitive function after traumatic brain injury; the scheme is as follows: 1. Materials and Methods: 1.1 Experimental Animals and Grouping: 120 clean-grade healthy male C57BL / 6 mice, 6-8 weeks old and weighing 18-24g, were provided by the Experimental Animal Center of Daping Hospital, Army Medical University [Animal Production License No.: SCXK (Beijing) 2024-0001, Animal Use License No.: SYXK (Chongqing) 2022-0003]. The experiment was approved by the Ethics Committee of Army Medical University (No. AMUWEC20237402). Following the conditions recommended by the International Association for Assessment and Certification of Laboratory Animal Care, a 12 / 12h light / dark cycle was maintained, with free access to food and water. Mice were randomly divided into four groups: control group (C group), high-altitude exposure group (H group), high-altitude exposure + impact injury group (HB group), and high-altitude exposure + impact injury + lung protection group (HP group), with 30 mice in each group (10 mice each on days 1, 3, and 7 post-injury). Eight mice died due to the impact, with no replacements.

[0022] 1.2 Preparation of acute high-altitude exposure hypoxia model: Animals were fasted and given free access to water for 12 hours before modeling. The H group, HB group, HP group and HB+TrkB+ group were placed in a hypobaric chamber (Tawang Technology: mProOx-810L) to simulate an altitude of 4000 meters, with an ascent time of 30 minutes and an exposure time of 24 hours.

[0023] 1.3 Preparation of an acute high-altitude exposure shock injury model: After the hypoxic exposure, mice were removed from the hypobaric chamber and immediately anesthetized in the HB, HP, and HB+TrkB+ groups (0.1% sodium pentobarbital, 30 mg / kg). Mice in the HB and HB+TrkB+ groups were fixed in specially designed cages and reinforced with straps. Mice in the HP group had their torsos fixed with a rigid torso brace coated with polyurea (only the head was exposed). The brace was then riveted to the iron cage and fixed to an iron frame. Mice were placed in the right lateral decubitus position, and a shock injury model was prepared using a BST-I type bio-shock tube (driving pressure 4.0 MPa). Figure 1 Group C was fed at normal pressure and oxygen throughout the entire period. Lung function and behavioral tests were performed at 24, 72, and 168 hours after the impact injury.

[0024] 1.4 Preparation of Polyurea Protective Equipment: Prepare two hollow steel sleeves with diameters of 5cm and 2.5cm respectively. Overlap the centers of the steel sleeves of different sizes. Figure 1 d) Pour polyurea material into the surrounding space and place it in a ventilated area for 2-4 days to allow it to solidify.

[0025] 1.5 Lung Function Testing: Lung function was tested using a whole-body plethysmograph (WBP) system at 24h, 72h, and 168h after the impact injury. Mice were placed in a closed WBP chamber and allowed to acclimatize to the temperature-controlled, quiet environment for 15 minutes before testing began. Changes in airflow caused by thoracic and abdominal respiratory movements were converted into electrical signals by pressure sensors within the chamber. The respiratory curves were then analyzed by a computer to obtain inspiratory time (TI), expiratory time (TE), relaxation time (TR), and minute ventilation volume (MV).

[0026] 1.6 Elevated Plus Maze (EPM): Animals were placed in a maze consisting of two 30cm long and 6cm wide open-arm track and two 30cm long and 6cm wide closed-arm platform. The activity time and distance of mice in the closed and open arms were observed, and the ratio of open-arm time and open-arm distance were calculated.

[0027] 1.7 Western blot analysis: After weighing the hippocampal tissue, add lysis buffer containing phosphatase and protease inhibitors. 10 mL of lysis buffer containing phosphatase and protease inhibitors is required per 1 g of tissue. Cut the tissue blocks into small pieces, sonicate for 5 min, centrifuge at 14000×g for 20 min, collect the supernatant, determine protein concentration using the BCA method, add loading buffer, boil for 10 min, aliquot, and store at -80℃.

[0028] Take 10 μL of protein sample for SDS-PAGE gel electrophoresis, use PVDF membrane wet transfer, and block on a shaker with 5% skim milk powder for 90 min. Primary antibodies were incubated overnight on a shaker at 4°C: rabbit anti-BDNF antibody (1:1000; Abcam, UK, ab108319), rabbit anti-P-PI3K antibody (1:1000; Cell Signaling Technology, USA, Y458), rabbit anti-PI3K antibody (1:1000; Cell Signaling Technology, USA, 19H8), rabbit anti-P-AKT antibody (1:1000; Cell Signaling Technology, USA, S473), rabbit anti-AKT antibody (1:1000; Cell Signaling Technology, USA, C26E7), mouse anti-PSD95 antibody (1:1000; Cell Signaling Technology, USA, 7E3), and rabbit anti-β-actin (1:10000; Wuhan Sanying Biotechnology Co., Ltd.). The next day, the rabbit was washed three times on a TBST shaker for 8 minutes each time. Secondary antibodies were prepared: donkey anti-rabbit (1:10000, Jackson Laboratories, USA) and donkey anti-mouse (1:1:10000). (10000, Jackson Laboratories, USA) Incubated at room temperature for 1 hour, washed 3 times on a TBST shaker, then developed using ECL chemiluminescence imaging, and scanned and imaged using a protein imager (Tanon, 4600SF). ImageJ was used for quantitative analysis of gray values, and the ratio of gray values ​​of the target protein to the internal control protein (β-actin) was used as the expression level of the target protein.

[0029] 1.8 Immunofluorescence staining: Brain tissue was fixed by immersion in 4% PFA solution at 4℃ for 24-48 hours, then dehydrated in 18%, 24%, and 30% sucrose solutions for 1, 1, and 2 days respectively, until the tissue settled. It was then embedded using OCT tissue embedding medium (4583, SaKuRa, USA), and frozen sections (18μm) were prepared along the coronal plane of the brain and hippocampus (CryoStar NX50, Thermo Fisher Scientific, China). For immunofluorescence staining, the sections were warmed at room temperature for 30 minutes, washed with PBS for 8 minutes × 3 times, permeabilized with 0.3% Triton X-100 for 30 minutes, and washed with PBS for 8 minutes × 3 times. Immunostaining blocking solution was added and incubated for 60 minutes. The liquid was aspirated, and primary antibody (Anti-SYN1, 1:200) was added and incubated overnight at 4℃. The next day, the slides were warmed in the room for 30 minutes, the primary antibody was removed, and the slides were washed with PBS for 8 minutes each time. The corresponding fluorescent secondary antibody was added, and the slides were incubated at room temperature for 1 hour. The slides were then washed with PBS for 8 minutes each time, and DAPI was added and incubated for 3 minutes. The slides were then washed with PBS for 8 minutes each time. After the tissue was dried, anti-quenching mounting medium was added, and the slides were observed and photographed under a microscope.

[0030] 1.9 Statistical Analysis: Quantitative data were expressed as mean ± standard deviation (SD). The graphs are represented by () and plotted using GraphPad 10.4.1. Except for the comparisons between groups at different time points using two-way ANOVA for lung function indicators, PSD95, and BDNF protein expression grayscale values, all other data were analyzed using one-way ANOVA. P < 0.05 was considered statistically significant.

[0031] 2. Results: 2.1 Changes in lung function In group H, the TI was longer than that in group C at 1 day post-injury (P < 0.05), and the MV was lower than that in group C (P < 0.001). Compared with group H, group HB had longer TI, TE, and TR at 1, 3, and 7 days post-injury (P < 0.05), and significantly lower MV (P < 0.01). Compared with group HB, group HP had significantly shorter TI, TE, and TR at 1, 3, and 7 days post-injury (P < 0.05), and higher MV (P < 0.05). Figure 1 As shown, Figure 1 In the table, a: inspiratory time (TI); b: expiratory time (TE); c: relaxation time (TR); d: minute ventilation (MV); ***P<0.001, *P<0.05, H group vs C group (n=6); ***P<0.001, **P<0.01, *P<0.05, HB group vs H group (n=6); ***P<0.001, **P<0.01, *P<0.05, HP group vs HB group (n=6).

[0032] 2.2 Changes in cognitive function The results of the elevated cross maze test showed that the opening arm time ratio and opening arm distance ratio of groups H, HB, and HP were all lower than those of group C at 1 day, 3 days, and 7 days. Compared with group C, the time ratio of group H at 1 day was significantly lower than that of group C (P < 0.001). Compared with group H, the time ratio of group HB at 3 days was significantly lower than that of group H (P < 0.05).

[0033] like Figure 2 As shown, Figure 2 In the diagram, ad represents the elevated cross maze trajectory diagrams of the control group (C group), the high-altitude exposure group (H group), the high-altitude exposure + impact injury group (HB group), and the high-altitude exposure + impact injury + lung protection group (HP group), respectively; e: time ratio 1 day after injury; f: distance ratio 1 day after injury; g: time ratio 3 days after injury; h: distance ratio 3 days after injury; i: time ratio 7 days after injury; j: distance ratio 7 days after injury; ****P < 0.0001, ***P < 0.001, **P < 0.01, *P < 0.05, vs. C group (n=8); *P < 0.05, HB group vs. H group (n=8).

[0034] 2.3 Expression of molecules related to synaptic plasticity At 1, 3, and 7 days post-injury, the expression levels of BDNF and PSD95 in the brain tissues of groups H, HB, and HP were all lower than those in group C. BDNF expression in group H was significantly lower than in group C at 1 day, but significantly higher than in group HB; PSD95 expression was significantly higher than in group HB at 1, 3, and 7 days, while PSD95 in group HB was significantly lower than in groups C, H, and HP; BDNF was significantly lower than in groups C, H, and HP only at 1 day, and significantly lower than in group C at 3 and 7 days.

[0035] like Figure 3 As shown, Figure 3 In the study, the groups were: control group (C group), high-altitude exposure group (H group), high-altitude exposure + brain concussion injury group (HB group), and high-altitude exposure + concussion injury + lung protection group (HP group); a, b, c: Western blot results; d: PSD95 protein OD value; e: BDNF protein OD value; ****P<0.0001, ***P<0.001, **P<0.01, *P<0.05, vs C group (n=3); ****P<0.0001, ***P<0.001, **P<0.01, HB vs H group (n=3); **P<0.01, *P<0.05, HP vs HB group (n=3).

[0036] Immunofluorescence staining was performed 3 days post-injury to detect SYN1 expression in the DG region. The expression levels in groups H and HP were lower than in group C, but higher than in group HB. Group HB showed significantly weaker fluorescence intensity than the other three groups, and its SYN1 expression level was lower than the other three groups.

[0037] like Figure 4 As shown, Figure 4 The study included a control group (Group C), a high-altitude exposure group (Group H), a high-altitude exposure + brain trauma group (Group HB), and a high-altitude exposure + trauma + lung protection group (Group HP). Immunofluorescence was used to detect DAPI (blue), Neun (green), and SYN1 (red).

[0038] 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. A chest protector for mitigating cognitive dysfunction from concussive brain injury, characterized by, The chest protection device comprises: a rigid protective shell, which is shaped to cover the main area of the subject's torso; an energy dissipation core, which is carried by the rigid protective shell and is made of polyurea polymer, for absorbing and dissipating impact energy through material deformation and stress dispersion when subjected to shock wave load; a fixing component, which is connected to the rigid protective shell, for stably fixing the chest protection device to the subject's torso and exposing the head.

2. The thoracic protection device of claim 1, wherein, The main area is the chest and abdomen.

3. The thoracic protection device of claim 2, wherein, The rigid protective shell is composed of an inner steel sleeve and an outer steel sleeve, and the polyurea polymer is poured into the annular space between the inner and outer sleeves to form a composite structure after solidification.

4. The thoracic protection device of claim 3, wherein, The protection device is configured to reduce lung injury caused by shock waves after exposure to a low-pressure and low-oxygen environment, thereby indirectly improving secondary brain injury and cognitive dysfunction caused by it.

5. A method of manufacturing a chest protector according to any one of claims 1-4, c h a r a c t e r i s e d in that The method comprises the following steps: providing a mold with a cavity adapted to the contour of the torso; pouring a polyurea polymer precursor mixture into the mold; polymer solidification under controlled temperature and ventilation conditions to form an energy dissipation core; integrating the solidified core with the rigid protective shell and installing the fixing component.

6. A method of applying chest protection to improve cognitive function following a concussive brain injury, characterized by, The method comprises the following steps: a pretreatment step: exposing the subject to low-pressure and low-oxygen conditions simulating a high-altitude environment for a set time; a shock application step: immediately after the pretreatment step, applying a shock wave load with set parameters to the subject; a protection step: at least during the shock application step, wearing the chest protection device as claimed in any one of claims 1-4 to protect the chest and abdomen of the subject from direct impact injury.

7. The method of claim 6, wherein, In the pretreatment step, the simulated altitude in the low-pressure and low-oxygen conditions is 3000-5000 meters, and the exposure time is 12-48 hours; in the shock application step, the peak overpressure of the shock wave is 300-500 kPa.

8. A composition for treating or preventing secondary cognitive impairment following an impact brain injury, characterized in that, The composition comprises an agent capable of enhancing the activity of the brain-derived neurotrophic factor signaling pathway, and is designed to be used in combination with the method as claimed in any one of claims 5-7 to synergistically promote the expression of hippocampal synaptic plasticity-related proteins.

9. The composition of claim 8, wherein, The brain-derived neurotrophic factor signaling pathway is the BDNF / TrkB-PI3K-AKT-mTOR pathway, and the synaptic plasticity-related proteins include PSD95 and SYN1.

10. A method for constructing an animal model for assessing the protective effect of chest protection on cognitive function after impact brain injury, characterized by, The method comprises: animal selection: selecting healthy adult male C57BL / 6 mice; high altitude exposure modeling: placing the mice in a low-pressure oxygen chamber to simulate a 4000-meter altitude environment for 24 hours to establish an acute high altitude exposure model; impact injury modeling: after high altitude exposure, immediately fix the mice in a standard right lateral position, use a biological shock tube to apply an impact wave with a driving pressure of 4.0 MPa to establish a torso impact injury model; protection intervention group setting: before the impact, the experimental group mice are worn with the chest protection device as claimed in any one of claims 1-3, while the model group mice are not worn, to construct animal models for comparative evaluation of protection intervention.

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